THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL

THE PROTECTIVE EFFECT OF APOCYNIN ON A... | F1000Research "use strict";function _typeof(t){return(_typeof="function"==typeof Symbol&&"symbol"==typeof Symbol.iterator?function(t){return typeof t}:function(t){return t&&"function"==typeof Symbol&&t.constructor===Symbol&&t!==Symbol.prototype?"symbol":typeof t})(t)}!function(){var t=function(){var t,e,o=[],n=window,r=n;for(;r;){try{if(r.frames.__tcfapiLocator){t=r;break}}catch(t){}if(r===n.top)break;r=r.parent}t||(!function t(){var e=n.document,o=!!n.frames.__tcfapiLocator;if(!o)if(e.body){var r=e.createElement("iframe");r.style.cssText="display:none",r.name="__tcfapiLocator",e.body.appendChild(r)}else setTimeout(t,5);return!o}(),n.__tcfapi=function(){for(var t=arguments.length,n=new Array(t),r=0;r 3&&2===parseInt(n[1],10)&&"boolean"==typeof n[3]&&(e=n[3],"function"==typeof n[2]&&n[2]("set",!0)):"ping"===n[0]?"function"==typeof n[2]&&n[2]({gdprApplies:e,cmpLoaded:!1,cmpStatus:"stub"}):o.push(n)},n.addEventListener("message",(function(t){var e="string"==typeof t.data,o={};if(e)try{o=JSON.parse(t.data)}catch(t){}else o=t.data;var n="object"===_typeof(o)&&null!==o?o.__tcfapiCall:null;n&&window.__tcfapi(n.command,n.version,(function(o,r){var a={__tcfapiReturn:{returnValue:o,success:r,callId:n.callId}};t&&t.source&&t.source.postMessage&&t.source.postMessage(e?JSON.stringify(a):a,"*")}),n.parameter)}),!1))};"undefined"!=typeof module?module.exports=t:t()}(); dataLayer = dataLayer || []; // Standard GTM initialization - Google Consent Mode handles consent automatically (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl+ '>m_auth=hzk0Vc3qFsQYhCrIoHz68A>m_preview=env-1>m_cookies_win=x';f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-MWFK8L5J'); ;window.NREUM||(NREUM={});NREUM.init={distributed_tracing:{enabled:true},privacy:{cookies_enabled:true},ajax:{deny_list:["bam.nr-data.net"]}}; ;NREUM.loader_config={accountID:"438030",trustKey:"438030",agentID:"772317073",licenseKey:"97f8f67f26",applicationID:"772317073"} ;NREUM.info={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net",licenseKey:"97f8f67f26",applicationID:"772317073",sa:1} ;/*! For license information please see nr-loader-spa-1.236.0.min.js.LICENSE.txt */ (()=>{"use strict";var e,t,r={5763:(e,t,r)=>{r.d(t,{P_:()=>l,Mt:()=>g,C5:()=>s,DL:()=>v,OP:()=>T,lF:()=>D,Yu:()=>y,Dg:()=>h,CX:()=>c,GE:()=>b,sU:()=>_});var n=r(8632),i=r(9567);const o={beacon:n.ce.beacon,errorBeacon:n.ce.errorBeacon,licenseKey:void 0,applicationID:void 0,sa:void 0,queueTime:void 0,applicationTime:void 0,ttGuid:void 0,user:void 0,account:void 0,product:void 0,extra:void 0,jsAttributes:{},userAttributes:void 0,atts:void 0,transactionName:void 0,tNamePlain:void 0},a={};function s(e){if(!e)throw new Error("All info objects require an agent identifier!");if(!a[e])throw new Error("Info for ".concat(e," was never set"));return a[e]}function c(e,t){if(!e)throw new Error("All info objects require an agent identifier!");a[e]=(0,i.D)(t,o),(0,n.Qy)(e,a[e],"info")}var u=r(7056);const d=()=>{const e={blockSelector:"[data-nr-block]",maskInputOptions:{password:!0}};return{allow_bfcache:!0,privacy:{cookies_enabled:!0},ajax:{deny_list:void 0,enabled:!0,harvestTimeSeconds:10},distributed_tracing:{enabled:void 0,exclude_newrelic_header:void 0,cors_use_newrelic_header:void 0,cors_use_tracecontext_headers:void 0,allowed_origins:void 0},session:{domain:void 0,expiresMs:u.oD,inactiveMs:u.Hb},ssl:void 0,obfuscate:void 0,jserrors:{enabled:!0,harvestTimeSeconds:10},metrics:{enabled:!0},page_action:{enabled:!0,harvestTimeSeconds:30},page_view_event:{enabled:!0},page_view_timing:{enabled:!0,harvestTimeSeconds:30,long_task:!1},session_trace:{enabled:!0,harvestTimeSeconds:10},harvest:{tooManyRequestsDelay:60},session_replay:{enabled:!1,harvestTimeSeconds:60,sampleRate:.1,errorSampleRate:.1,maskTextSelector:"*",maskAllInputs:!0,get blockClass(){return"nr-block"},get ignoreClass(){return"nr-ignore"},get maskTextClass(){return"nr-mask"},get blockSelector(){return e.blockSelector},set blockSelector(t){e.blockSelector+=",".concat(t)},get maskInputOptions(){return e.maskInputOptions},set maskInputOptions(t){e.maskInputOptions={...t,password:!0}}},spa:{enabled:!0,harvestTimeSeconds:10}}},f={};function l(e){if(!e)throw new Error("All configuration objects require an agent identifier!");if(!f[e])throw new Error("Configuration for ".concat(e," was never set"));return f[e]}function h(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");f[e]=(0,i.D)(t,d()),(0,n.Qy)(e,f[e],"config")}function g(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");var r=l(e);if(r){for(var n=t.split("."),i=0;i {r.d(t,{D:()=>i});var n=r(50);function i(e,t){try{if(!e||"object"!=typeof e)return(0,n.Z)("Setting a Configurable requires an object as input");if(!t||"object"!=typeof t)return(0,n.Z)("Setting a Configurable requires a model to set its initial properties");const r=Object.create(Object.getPrototypeOf(t),Object.getOwnPropertyDescriptors(t)),o=0===Object.keys(r).length?e:r;for(let a in o)if(void 0!==e[a])try{"object"==typeof e[a]&&"object"==typeof t[a]?r[a]=i(e[a],t[a]):r[a]=e[a]}catch(e){(0,n.Z)("An error occurred while setting a property of a Configurable",e)}return r}catch(e){(0,n.Z)("An error occured while setting a Configurable",e)}}},6818:(e,t,r)=>{r.d(t,{Re:()=>i,gF:()=>o,q4:()=>n});const n="1.236.0",i="PROD",o="CDN"},385:(e,t,r)=>{r.d(t,{FN:()=>a,IF:()=>u,Nk:()=>f,Tt:()=>s,_A:()=>o,il:()=>n,pL:()=>c,v6:()=>i,w1:()=>d});const n="undefined"!=typeof window&&!!window.document,i="undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self.navigator instanceof WorkerNavigator||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis.navigator instanceof WorkerNavigator),o=n?window:"undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis),a=""+o?.location,s=/iPad|iPhone|iPod/.test(navigator.userAgent),c=s&&"undefined"==typeof SharedWorker,u=(()=>{const e=navigator.userAgent.match(/Firefox[/\s](\d+\.\d+)/);return Array.isArray(e)&&e.length>=2?+e[1]:0})(),d=Boolean(n&&window.document.documentMode),f=!!navigator.sendBeacon},1117:(e,t,r)=>{r.d(t,{w:()=>o});var n=r(50);const i={agentIdentifier:"",ee:void 0};class o{constructor(e){try{if("object"!=typeof e)return(0,n.Z)("shared context requires an object as input");this.sharedContext={},Object.assign(this.sharedContext,i),Object.entries(e).forEach((e=>{let[t,r]=e;Object.keys(i).includes(t)&&(this.sharedContext[t]=r)}))}catch(e){(0,n.Z)("An error occured while setting SharedContext",e)}}}},8e3:(e,t,r)=>{r.d(t,{L:()=>d,R:()=>c});var n=r(2177),i=r(1284),o=r(4322),a=r(3325);const s={};function c(e,t){const r={staged:!1,priority:a.p[t]||0};u(e),s[e].get(t)||s[e].set(t,r)}function u(e){e&&(s[e]||(s[e]=new Map))}function d(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:"",t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:"feature";if(u(e),!e||!s[e].get(t))return a(t);s[e].get(t).staged=!0;const r=[...s[e]];function a(t){const r=e?n.ee.get(e):n.ee,a=o.X.handlers;if(r.backlog&&a){var s=r.backlog[t],c=a[t];if(c){for(var u=0;s&&u {let[t,r]=e;return r.staged}))&&(r.sort(((e,t)=>e[1].priority-t[1].priority)),r.forEach((e=>{let[t]=e;a(t)})))}function f(e,t){var r=e[1];(0,i.D)(t[r],(function(t,r){var n=e[0];if(r[0]===n){var i=r[1],o=e[3],a=e[2];i.apply(o,a)}}))}},2177:(e,t,r)=>{r.d(t,{c:()=>f,ee:()=>u});var n=r(8632),i=r(2210),o=r(1284),a=r(5763),s="nr@context";let c=(0,n.fP)();var u;function d(){}function f(e){return(0,i.X)(e,s,l)}function l(){return new d}function h(){u.aborted=!0,u.backlog={}}c.ee?u=c.ee:(u=function e(t,r){var n={},c={},f={},g=!1;try{g=16===r.length&&(0,a.OP)(r).isolatedBacklog}catch(e){}var p={on:b,addEventListener:b,removeEventListener:y,emit:v,get:x,listeners:w,context:m,buffer:A,abort:h,aborted:!1,isBuffering:E,debugId:r,backlog:g?{}:t&&"object"==typeof t.backlog?t.backlog:{}};return p;function m(e){return e&&e instanceof d?e:e?(0,i.X)(e,s,l):l()}function v(e,r,n,i,o){if(!1!==o&&(o=!0),!u.aborted||i){t&&o&&t.emit(e,r,n);for(var a=m(n),s=w(e),d=s.length,f=0;fn,p:()=>i});var n=r(2177).ee.get("handle");function i(e,t,r,i,o){o?(o.buffer([e],i),o.emit(e,t,r)):(n.buffer([e],i),n.emit(e,t,r))}},4322:(e,t,r)=>{r.d(t,{X:()=>o});var n=r(5546);o.on=a;var i=o.handlers={};function o(e,t,r,o){a(o||n.E,i,e,t,r)}function a(e,t,r,i,o){o||(o="feature"),e||(e=n.E);var a=t[o]=t[o]||{};(a[r]=a[r]||[]).push([e,i])}},3239:(e,t,r)=>{r.d(t,{bP:()=>s,iz:()=>c,m$:()=>a});var n=r(385);let i=!1,o=!1;try{const e={get passive(){return i=!0,!1},get signal(){return o=!0,!1}};n._A.addEventListener("test",null,e),n._A.removeEventListener("test",null,e)}catch(e){}function a(e,t){return i||o?{capture:!!e,passive:i,signal:t}:!!e}function s(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;window.addEventListener(e,t,a(r,n))}function c(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;document.addEventListener(e,t,a(r,n))}},4402:(e,t,r)=>{r.d(t,{Ht:()=>u,M:()=>c,Rl:()=>a,ky:()=>s});var n=r(385);const i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx";function o(e,t){return e?15&e[t]:16*Math.random()|0}function a(){const e=n._A?.crypto||n._A?.msCrypto;let t,r=0;return e&&e.getRandomValues&&(t=e.getRandomValues(new Uint8Array(31))),i.split("").map((e=>"x"===e?o(t,++r).toString(16):"y"===e?(3&o()|8).toString(16):e)).join("")}function s(e){const t=n._A?.crypto||n._A?.msCrypto;let r,i=0;t&&t.getRandomValues&&(r=t.getRandomValues(new Uint8Array(31)));const a=[];for(var s=0;s {r.d(t,{Bq:()=>n,Hb:()=>o,oD:()=>i});const n="NRBA",i=144e5,o=18e5},7894:(e,t,r)=>{function n(){return Math.round(performance.now())}r.d(t,{z:()=>n})},7243:(e,t,r)=>{r.d(t,{e:()=>o});var n=r(385),i={};function o(e){if(e in i)return i[e];if(0===(e||"").indexOf("data:"))return{protocol:"data"};let t;var r=n._A?.location,o={};if(n.il)t=document.createElement("a"),t.href=e;else try{t=new URL(e,r.href)}catch(e){return o}o.port=t.port;var a=t.href.split("://");!o.port&&a[1]&&(o.port=a[1].split("/")[0].split("@").pop().split(":")[1]),o.port&&"0"!==o.port||(o.port="https"===a[0]?"443":"80"),o.hostname=t.hostname||r.hostname,o.pathname=t.pathname,o.protocol=a[0],"/"!==o.pathname.charAt(0)&&(o.pathname="/"+o.pathname);var s=!t.protocol||":"===t.protocol||t.protocol===r.protocol,c=t.hostname===r.hostname&&t.port===r.port;return o.sameOrigin=s&&(!t.hostname||c),"/"===o.pathname&&(i[e]=o),o}},50:(e,t,r)=>{function n(e,t){"function"==typeof console.warn&&(console.warn("New Relic: ".concat(e)),t&&console.warn(t))}r.d(t,{Z:()=>n})},2587:(e,t,r)=>{r.d(t,{N:()=>c,T:()=>u});var n=r(2177),i=r(5546),o=r(8e3),a=r(3325);const s={stn:[a.D.sessionTrace],err:[a.D.jserrors,a.D.metrics],ins:[a.D.pageAction],spa:[a.D.spa],sr:[a.D.sessionReplay,a.D.sessionTrace]};function c(e,t){const r=n.ee.get(t);e&&"object"==typeof e&&(Object.entries(e).forEach((e=>{let[t,n]=e;void 0===u[t]&&(s[t]?s[t].forEach((e=>{n?(0,i.p)("feat-"+t,[],void 0,e,r):(0,i.p)("block-"+t,[],void 0,e,r),(0,i.p)("rumresp-"+t,[Boolean(n)],void 0,e,r)})):n&&(0,i.p)("feat-"+t,[],void 0,void 0,r),u[t]=Boolean(n))})),Object.keys(s).forEach((e=>{void 0===u[e]&&(s[e]?.forEach((t=>(0,i.p)("rumresp-"+e,[!1],void 0,t,r))),u[e]=!1)})),(0,o.L)(t,a.D.pageViewEvent))}const u={}},2210:(e,t,r)=>{r.d(t,{X:()=>i});var n=Object.prototype.hasOwnProperty;function i(e,t,r){if(n.call(e,t))return e[t];var i=r();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(e,t,{value:i,writable:!0,enumerable:!1}),i}catch(e){}return e[t]=i,i}},1284:(e,t,r)=>{r.d(t,{D:()=>n});const n=(e,t)=>Object.entries(e||{}).map((e=>{let[r,n]=e;return t(r,n)}))},4351:(e,t,r)=>{r.d(t,{P:()=>o});var n=r(2177);const i=()=>{const e=new WeakSet;return(t,r)=>{if("object"==typeof r&&null!==r){if(e.has(r))return;e.add(r)}return r}};function o(e){try{return JSON.stringify(e,i())}catch(e){try{n.ee.emit("internal-error",[e])}catch(e){}}}},3960:(e,t,r)=>{r.d(t,{K:()=>a,b:()=>o});var n=r(3239);function i(){return"undefined"==typeof document||"complete"===document.readyState}function o(e,t){if(i())return e();(0,n.bP)("load",e,t)}function a(e){if(i())return e();(0,n.iz)("DOMContentLoaded",e)}},8632:(e,t,r)=>{r.d(t,{EZ:()=>u,Qy:()=>c,ce:()=>o,fP:()=>a,gG:()=>d,mF:()=>s});var n=r(7894),i=r(385);const o={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net"};function a(){return i._A.NREUM||(i._A.NREUM={}),void 0===i._A.newrelic&&(i._A.newrelic=i._A.NREUM),i._A.NREUM}function s(){let e=a();return e.o||(e.o={ST:i._A.setTimeout,SI:i._A.setImmediate,CT:i._A.clearTimeout,XHR:i._A.XMLHttpRequest,REQ:i._A.Request,EV:i._A.Event,PR:i._A.Promise,MO:i._A.MutationObserver,FETCH:i._A.fetch}),e}function c(e,t,r){let i=a();const o=i.initializedAgents||{},s=o[e]||{};return Object.keys(s).length||(s.initializedAt={ms:(0,n.z)(),date:new Date}),i.initializedAgents={...o,[e]:{...s,[r]:t}},i}function u(e,t){a()[e]=t}function d(){return function(){let e=a();const t=e.info||{};e.info={beacon:o.beacon,errorBeacon:o.errorBeacon,...t}}(),function(){let e=a();const t=e.init||{};e.init={...t}}(),s(),function(){let e=a();const t=e.loader_config||{};e.loader_config={...t}}(),a()}},7956:(e,t,r)=>{r.d(t,{N:()=>i});var n=r(3239);function i(e){let t=arguments.length>1&&void 0!==arguments[1]&&arguments[1],r=arguments.length>2?arguments[2]:void 0,i=arguments.length>3?arguments[3]:void 0;return void(0,n.iz)("visibilitychange",(function(){if(t)return void("hidden"==document.visibilityState&&e());e(document.visibilityState)}),r,i)}},1214:(e,t,r)=>{r.d(t,{em:()=>v,u5:()=>N,QU:()=>S,_L:()=>I,Gm:()=>L,Lg:()=>M,gy:()=>U,BV:()=>Q,Kf:()=>ee});var n=r(2177);const i="nr@original";var o=Object.prototype.hasOwnProperty,a=!1;function s(e,t){return e||(e=n.ee),r.inPlace=function(e,t,n,i,o){n||(n="");var a,s,c,u="-"===n.charAt(0);for(c=0;c 2?n-2:0),o=2;o {r(A[T],e,w),r(E[T],e,w)})),r(l._A,"fetch",y),t.on(y+"end",(function(e,r){var n=this;if(r){var i=r.headers.get("content-length");null!==i&&(n.rxSize=i),t.emit(y+"done",[null,r],n)}else t.emit(y+"done",[e],n)})),t}const O={},j=["pushState","replaceState"];function S(e){const t=function(e){return(e||n.ee).get("history")}(e);return!l.il||O[t.debugId]++||(O[t.debugId]=1,s(t).inPlace(window.history,j,"-")),t}var P=r(3239);const C={},R=["appendChild","insertBefore","replaceChild"];function I(e){const t=function(e){return(e||n.ee).get("jsonp")}(e);if(!l.il||C[t.debugId])return t;C[t.debugId]=!0;var r=s(t),i=/[?&](?:callback|cb)=([^&#]+)/,o=/(.*)\.([^.]+)/,a=/^(\w+)(\.|$)(.*)$/;function c(e,t){var r=e.match(a),n=r[1],i=r[3];return i?c(i,t[n]):t[n]}return r.inPlace(Node.prototype,R,"dom-"),t.on("dom-start",(function(e){!function(e){if(!e||"string"!=typeof e.nodeName||"script"!==e.nodeName.toLowerCase())return;if("function"!=typeof e.addEventListener)return;var n=(a=e.src,s=a.match(i),s?s[1]:null);var a,s;if(!n)return;var u=function(e){var t=e.match(o);if(t&&t.length>=3)return{key:t[2],parent:c(t[1],window)};return{key:e,parent:window}}(n);if("function"!=typeof u.parent[u.key])return;var d={};function f(){t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}function l(){t.emit("jsonp-error",[],d),t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}r.inPlace(u.parent,[u.key],"cb-",d),e.addEventListener("load",f,(0,P.m$)(!1)),e.addEventListener("error",l,(0,P.m$)(!1)),t.emit("new-jsonp",[e.src],d)}(e[0])})),t}var k=r(5763);const H={};function L(e){const t=function(e){return(e||n.ee).get("mutation")}(e);if(!l.il||H[t.debugId])return t;H[t.debugId]=!0;var r=s(t),i=k.Yu.MO;return i&&(window.MutationObserver=function(e){return this instanceof i?new i(r(e,"fn-")):i.apply(this,arguments)},MutationObserver.prototype=i.prototype),t}const z={};function M(e){const t=function(e){return(e||n.ee).get("promise")}(e);if(z[t.debugId])return t;z[t.debugId]=!0;var r=n.c,o=s(t),a=k.Yu.PR;return a&&function(){function e(r){var n=t.context(),i=o(r,"executor-",n,null,!1);const s=Reflect.construct(a,[i],e);return t.context(s).getCtx=function(){return n},s}l._A.Promise=e,Object.defineProperty(e,"name",{value:"Promise"}),e.toString=function(){return a.toString()},Object.setPrototypeOf(e,a),["all","race"].forEach((function(r){const n=a[r];e[r]=function(e){let i=!1;[...e||[]].forEach((e=>{this.resolve(e).then(a("all"===r),a(!1))}));const o=n.apply(this,arguments);return o;function a(e){return function(){t.emit("propagate",[null,!i],o,!1,!1),i=i||!e}}}})),["resolve","reject"].forEach((function(r){const n=a[r];e[r]=function(e){const r=n.apply(this,arguments);return e!==r&&t.emit("propagate",[e,!0],r,!1,!1),r}})),e.prototype=a.prototype;const n=a.prototype.then;a.prototype.then=function(){var e=this,i=r(e);i.promise=e;for(var a=arguments.length,s=new Array(a),c=0;c e())),t};function m(e,t){i.inPlace(t,["onreadystatechange"],"fn-",E)}function b(){var e=this,t=r.context(e);e.readyState>3&&!t.resolved&&(t.resolved=!0,r.emit("xhr-resolved",[],e)),i.inPlace(e,f,"fn-",E)}if(function(e,t){for(var r in e)t[r]=e[r]}(o,p),p.prototype=o.prototype,i.inPlace(p.prototype,J,"-xhr-",E),r.on("send-xhr-start",(function(e,t){m(e,t),function(e){h.push(e),a&&(y?y.then(A):u?u(A):(w=-w,x.data=w))}(t)})),r.on("open-xhr-start",m),a){var y=c&&c.resolve();if(!u&&!c){var w=1,x=document.createTextNode(w);new a(A).observe(x,{characterData:!0})}}else t.on("fn-end",(function(e){e[0]&&e[0].type===d||A()}));function A(){for(var e=0;e {r.d(t,{t:()=>n});const n=r(3325).D.ajax},6660:(e,t,r)=>{r.d(t,{A:()=>i,t:()=>n});const n=r(3325).D.jserrors,i="nr@seenError"},3081:(e,t,r)=>{r.d(t,{gF:()=>o,mY:()=>i,t9:()=>n,vz:()=>s,xS:()=>a});const n=r(3325).D.metrics,i="sm",o="cm",a="storeSupportabilityMetrics",s="storeEventMetrics"},4649:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageAction},7633:(e,t,r)=>{r.d(t,{Dz:()=>i,OJ:()=>a,qw:()=>o,t9:()=>n});const n=r(3325).D.pageViewEvent,i="firstbyte",o="domcontent",a="windowload"},9251:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageViewTiming},3614:(e,t,r)=>{r.d(t,{BST_RESOURCE:()=>i,END:()=>s,FEATURE_NAME:()=>n,FN_END:()=>u,FN_START:()=>c,PUSH_STATE:()=>d,RESOURCE:()=>o,START:()=>a});const n=r(3325).D.sessionTrace,i="bstResource",o="resource",a="-start",s="-end",c="fn"+a,u="fn"+s,d="pushState"},7836:(e,t,r)=>{r.d(t,{BODY:()=>A,CB_END:()=>E,CB_START:()=>u,END:()=>x,FEATURE_NAME:()=>i,FETCH:()=>_,FETCH_BODY:()=>v,FETCH_DONE:()=>m,FETCH_START:()=>p,FN_END:()=>c,FN_START:()=>s,INTERACTION:()=>l,INTERACTION_API:()=>d,INTERACTION_EVENTS:()=>o,JSONP_END:()=>b,JSONP_NODE:()=>g,JS_TIME:()=>T,MAX_TIMER_BUDGET:()=>a,REMAINING:()=>f,SPA_NODE:()=>h,START:()=>w,originalSetTimeout:()=>y});var n=r(5763);const i=r(3325).D.spa,o=["click","submit","keypress","keydown","keyup","change"],a=999,s="fn-start",c="fn-end",u="cb-start",d="api-ixn-",f="remaining",l="interaction",h="spaNode",g="jsonpNode",p="fetch-start",m="fetch-done",v="fetch-body-",b="jsonp-end",y=n.Yu.ST,w="-start",x="-end",A="-body",E="cb"+x,T="jsTime",_="fetch"},5938:(e,t,r)=>{r.d(t,{W:()=>o});var n=r(5763),i=r(2177);class o{constructor(e,t,r){this.agentIdentifier=e,this.aggregator=t,this.ee=i.ee.get(e,(0,n.OP)(this.agentIdentifier).isolatedBacklog),this.featureName=r,this.blocked=!1}}},9144:(e,t,r)=>{r.d(t,{j:()=>m});var n=r(3325),i=r(5763),o=r(5546),a=r(2177),s=r(7894),c=r(8e3),u=r(3960),d=r(385),f=r(50),l=r(3081),h=r(8632);function g(){const e=(0,h.gG)();["setErrorHandler","finished","addToTrace","inlineHit","addRelease","addPageAction","setCurrentRouteName","setPageViewName","setCustomAttribute","interaction","noticeError","setUserId"].forEach((t=>{e[t]=function(){for(var r=arguments.length,n=new Array(r),i=0;i 1?r-1:0),i=1;i {e.exposed&&e.api[t]&&o.push(e.api[t](...n))})),o.length>1?o:o[0]}(t,...n)}}))}var p=r(2587);function m(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{},m=arguments.length>2?arguments[2]:void 0,v=arguments.length>3?arguments[3]:void 0,{init:b,info:y,loader_config:w,runtime:x={loaderType:m},exposed:A=!0}=t;const E=(0,h.gG)();y||(b=E.init,y=E.info,w=E.loader_config),(0,i.Dg)(e,b||{}),(0,i.GE)(e,w||{}),(0,i.sU)(e,x),y.jsAttributes??={},d.v6&&(y.jsAttributes.isWorker=!0),(0,i.CX)(e,y),g();const T=function(e,t){t||(0,c.R)(e,"api");const h={};var g=a.ee.get(e),p=g.get("tracer"),m="api-",v=m+"ixn-";function b(t,r,n,o){const a=(0,i.C5)(e);return null===r?delete a.jsAttributes[t]:(0,i.CX)(e,{...a,jsAttributes:{...a.jsAttributes,[t]:r}}),x(m,n,!0,o||null===r?"session":void 0)(t,r)}function y(){}["setErrorHandler","finished","addToTrace","inlineHit","addRelease"].forEach((e=>h[e]=x(m,e,!0,"api"))),h.addPageAction=x(m,"addPageAction",!0,n.D.pageAction),h.setCurrentRouteName=x(m,"routeName",!0,n.D.spa),h.setPageViewName=function(t,r){if("string"==typeof t)return"/"!==t.charAt(0)&&(t="/"+t),(0,i.OP)(e).customTransaction=(r||"http://custom.transaction")+t,x(m,"setPageViewName",!0)()},h.setCustomAttribute=function(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2];if("string"==typeof e){if(["string","number"].includes(typeof t)||null===t)return b(e,t,"setCustomAttribute",r);(0,f.Z)("Failed to execute setCustomAttribute.\nNon-null value must be a string or number type, but a type of was provided."))}else(0,f.Z)("Failed to execute setCustomAttribute.\nName must be a string type, but a type of was provided."))},h.setUserId=function(e){if("string"==typeof e||null===e)return b("enduser.id",e,"setUserId",!0);(0,f.Z)("Failed to execute setUserId.\nNon-null value must be a string type, but a type of was provided."))},h.interaction=function(){return(new y).get()};var w=y.prototype={createTracer:function(e,t){var r={},i=this,a="function"==typeof t;return(0,o.p)(v+"tracer",[(0,s.z)(),e,r],i,n.D.spa,g),function(){if(p.emit((a?"":"no-")+"fn-start",[(0,s.z)(),i,a],r),a)try{return t.apply(this,arguments)}catch(e){throw p.emit("fn-err",[arguments,this,"string"==typeof e?new Error(e):e],r),e}finally{p.emit("fn-end",[(0,s.z)()],r)}}}};function x(e,t,r,i){return function(){return(0,o.p)(l.xS,["API/"+t+"/called"],void 0,n.D.metrics,g),i&&(0,o.p)(e+t,[(0,s.z)(),...arguments],r?null:this,i,g),r?void 0:this}}function A(){r.e(439).then(r.bind(r,7438)).then((t=>{let{setAPI:r}=t;r(e),(0,c.L)(e,"api")})).catch((()=>(0,f.Z)("Downloading runtime APIs failed...")))}return["actionText","setName","setAttribute","save","ignore","onEnd","getContext","end","get"].forEach((e=>{w[e]=x(v,e,void 0,n.D.spa)})),h.noticeError=function(e,t){"string"==typeof e&&(e=new Error(e)),(0,o.p)(l.xS,["API/noticeError/called"],void 0,n.D.metrics,g),(0,o.p)("err",[e,(0,s.z)(),!1,t],void 0,n.D.jserrors,g)},d.il?(0,u.b)((()=>A()),!0):A(),h}(e,v);return(0,h.Qy)(e,T,"api"),(0,h.Qy)(e,A,"exposed"),(0,h.EZ)("activatedFeatures",p.T),T}},3325:(e,t,r)=>{r.d(t,{D:()=>n,p:()=>i});const n={ajax:"ajax",jserrors:"jserrors",metrics:"metrics",pageAction:"page_action",pageViewEvent:"page_view_event",pageViewTiming:"page_view_timing",sessionReplay:"session_replay",sessionTrace:"session_trace",spa:"spa"},i={[n.pageViewEvent]:1,[n.pageViewTiming]:2,[n.metrics]:3,[n.jserrors]:4,[n.ajax]:5,[n.sessionTrace]:6,[n.pageAction]:7,[n.spa]:8,[n.sessionReplay]:9}}},n={};function i(e){var t=n[e];if(void 0!==t)return t.exports;var o=n[e]={exports:{}};return r[e](o,o.exports,i),o.exports}i.m=r,i.d=(e,t)=>{for(var r in t)i.o(t,r)&&!i.o(e,r)&&Object.defineProperty(e,r,{enumerable:!0,get:t[r]})},i.f={},i.e=e=>Promise.all(Object.keys(i.f).reduce(((t,r)=>(i.f[r](e,t),t)),[])),i.u=e=>(({78:"page_action-aggregate",147:"metrics-aggregate",242:"session-manager",317:"jserrors-aggregate",348:"page_view_timing-aggregate",412:"lazy-feature-loader",439:"async-api",538:"recorder",590:"session_replay-aggregate",675:"compressor",733:"session_trace-aggregate",786:"page_view_event-aggregate",873:"spa-aggregate",898:"ajax-aggregate"}[e]||e)+"."+{78:"ac76d497",147:"3dc53903",148:"1a20d5fe",242:"2a64278a",317:"49e41428",348:"bd6de33a",412:"2f55ce66",439:"30bd804e",538:"1b18459f",590:"cf0efb30",675:"ae9f91a8",733:"83105561",786:"06482edd",860:"03a8b7a5",873:"e6b09d52",898:"998ef92b"}[e]+"-1.236.0.min.js"),i.o=(e,t)=>Object.prototype.hasOwnProperty.call(e,t),e={},t="NRBA:",i.l=(r,n,o,a)=>{if(e[r])e[r].push(n);else{var s,c;if(void 0!==o)for(var u=document.getElementsByTagName("script"),d=0;d {s.onerror=s.onload=null,clearTimeout(h);var i=e[r];if(delete e[r],s.parentNode&&s.parentNode.removeChild(s),i&&i.forEach((e=>e(n))),t)return t(n)},h=setTimeout(l.bind(null,void 0,{type:"timeout",target:s}),12e4);s.onerror=l.bind(null,s.onerror),s.onload=l.bind(null,s.onload),c&&document.head.appendChild(s)}},i.r=e=>{"undefined"!=typeof Symbol&&Symbol.toStringTag&&Object.defineProperty(e,Symbol.toStringTag,{value:"Module"}),Object.defineProperty(e,"__esModule",{value:!0})},i.j=364,i.p="https://js-agent.newrelic.com/",(()=>{var e={364:0,953:0};i.f.j=(t,r)=>{var n=i.o(e,t)?e[t]:void 0;if(0!==n)if(n)r.push(n[2]);else{var o=new Promise(((r,i)=>n=e[t]=[r,i]));r.push(n[2]=o);var a=i.p+i.u(t),s=new Error;i.l(a,(r=>{if(i.o(e,t)&&(0!==(n=e[t])&&(e[t]=void 0),n)){var o=r&&("load"===r.type?"missing":r.type),a=r&&r.target&&r.target.src;s.message="Loading chunk "+t+" failed.\n("+o+": "+a+")",s.name="ChunkLoadError",s.type=o,s.request=a,n[1](s)}}),"chunk-"+t,t)}};var t=(t,r)=>{var n,o,[a,s,c]=r,u=0;if(a.some((t=>0!==e[t]))){for(n in s)i.o(s,n)&&(i.m[n]=s[n]);if(c)c(i)}for(t&&t(r);u {i.r(o);var e=i(3325),t=i(5763);const r=Object.values(e.D);function n(e){const n={};return r.forEach((r=>{n[r]=function(e,r){return!1!==(0,t.Mt)(r,"".concat(e,".enabled"))}(r,e)})),n}var a=i(9144);var s=i(5546),c=i(385),u=i(8e3),d=i(5938),f=i(3960),l=i(50);class h extends d.W{constructor(e,t,r){let n=!(arguments.length>3&&void 0!==arguments[3])||arguments[3];super(e,t,r),this.auto=n,this.abortHandler,this.featAggregate,this.onAggregateImported,n&&(0,u.R)(e,r)}importAggregator(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:{};if(this.featAggregate||!this.auto)return;const r=c.il&&!0===(0,t.Mt)(this.agentIdentifier,"privacy.cookies_enabled");let n;this.onAggregateImported=new Promise((e=>{n=e}));const o=async()=>{let t;try{if(r){const{setupAgentSession:e}=await Promise.all([i.e(860),i.e(242)]).then(i.bind(i,3228));t=e(this.agentIdentifier)}}catch(e){(0,l.Z)("A problem occurred when starting up session manager. This page will not start or extend any session.",e)}try{if(!this.shouldImportAgg(this.featureName,t))return void(0,u.L)(this.agentIdentifier,this.featureName);const{lazyFeatureLoader:r}=await i.e(412).then(i.bind(i,8582)),{Aggregate:o}=await r(this.featureName,"aggregate");this.featAggregate=new o(this.agentIdentifier,this.aggregator,e),n(!0)}catch(e){(0,l.Z)("Downloading and initializing ".concat(this.featureName," failed..."),e),this.abortHandler?.(),n(!1)}};c.il?(0,f.b)((()=>o()),!0):o()}shouldImportAgg(r,n){return r!==e.D.sessionReplay||!1!==(0,t.Mt)(this.agentIdentifier,"session_trace.enabled")&&(!!n?.isNew||!!n?.state.sessionReplay)}}var g=i(7633),p=i(7894);class m extends h{static featureName=g.t9;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];if(super(r,n,g.t9,i),("undefined"==typeof PerformanceNavigationTiming||c.Tt)&&"undefined"!=typeof PerformanceTiming){const n=(0,t.OP)(r);n[g.Dz]=Math.max(Date.now()-n.offset,0),(0,f.K)((()=>n[g.qw]=Math.max((0,p.z)()-n[g.Dz],0))),(0,f.b)((()=>{const t=(0,p.z)();n[g.OJ]=Math.max(t-n[g.Dz],0),(0,s.p)("timing",["load",t],void 0,e.D.pageViewTiming,this.ee)}))}this.importAggregator()}}var v=i(1117),b=i(1284);class y extends v.w{constructor(e){super(e),this.aggregatedData={}}store(e,t,r,n,i){var o=this.getBucket(e,t,r,i);return o.metrics=function(e,t){t||(t={count:0});return t.count+=1,(0,b.D)(e,(function(e,r){t[e]=w(r,t[e])})),t}(n,o.metrics),o}merge(e,t,r,n,i){var o=this.getBucket(e,t,n,i);if(o.metrics){var a=o.metrics;a.count+=r.count,(0,b.D)(r,(function(e,t){if("count"!==e){var n=a[e],i=r[e];i&&!i.c?a[e]=w(i.t,n):a[e]=function(e,t){if(!t)return e;t.c||(t=x(t.t));return t.min=Math.min(e.min,t.min),t.max=Math.max(e.max,t.max),t.t+=e.t,t.sos+=e.sos,t.c+=e.c,t}(i,a[e])}}))}else o.metrics=r}storeMetric(e,t,r,n){var i=this.getBucket(e,t,r);return i.stats=w(n,i.stats),i}getBucket(e,t,r,n){this.aggregatedData[e]||(this.aggregatedData[e]={});var i=this.aggregatedData[e][t];return i||(i=this.aggregatedData[e][t]={params:r||{}},n&&(i.custom=n)),i}get(e,t){return t?this.aggregatedData[e]&&this.aggregatedData[e][t]:this.aggregatedData[e]}take(e){for(var t={},r="",n=!1,i=0;i t.max&&(t.max=e),e 2&&void 0!==arguments[2])||arguments[2];super(e,r,j.t,n),c.il&&((0,t.OP)(e).initHidden=Boolean("hidden"===document.visibilityState),(0,N.N)((()=>(0,s.p)("docHidden",[(0,p.z)()],void 0,j.t,this.ee)),!0),(0,O.bP)("pagehide",(()=>(0,s.p)("winPagehide",[(0,p.z)()],void 0,j.t,this.ee))),this.importAggregator())}}var P=i(3081);class C extends h{static featureName=P.t9;constructor(e,t){let r=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(e,t,P.t9,r),this.importAggregator()}}var R,I=i(2210),k=i(1214),H=i(2177),L={};try{R=localStorage.getItem("__nr_flags").split(","),console&&"function"==typeof console.log&&(L.console=!0,-1!==R.indexOf("dev")&&(L.dev=!0),-1!==R.indexOf("nr_dev")&&(L.nrDev=!0))}catch(e){}function z(e){try{L.console&&z(e)}catch(e){}}L.nrDev&&H.ee.on("internal-error",(function(e){z(e.stack)})),L.dev&&H.ee.on("fn-err",(function(e,t,r){z(r.stack)})),L.dev&&(z("NR AGENT IN DEVELOPMENT MODE"),z("flags: "+(0,b.D)(L,(function(e,t){return e})).join(", ")));var M=i(6660);class B extends h{static featureName=M.t;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(r,n,M.t,i),this.skipNext=0;try{this.removeOnAbort=new AbortController}catch(e){}const o=this;o.ee.on("fn-start",(function(e,t,r){o.abortHandler&&(o.skipNext+=1)})),o.ee.on("fn-err",(function(t,r,n){o.abortHandler&&!n[M.A]&&((0,I.X)(n,M.A,(function(){return!0})),this.thrown=!0,(0,s.p)("err",[n,(0,p.z)()],void 0,e.D.jserrors,o.ee))})),o.ee.on("fn-end",(function(){o.abortHandler&&!this.thrown&&o.skipNext>0&&(o.skipNext-=1)})),o.ee.on("internal-error",(function(t){(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,o.ee)})),this.origOnerror=c._A.onerror,c._A.onerror=this.onerrorHandler.bind(this),c._A.addEventListener("unhandledrejection",(t=>{const r=function(e){let t="Unhandled Promise Rejection: ";if(e instanceof Error)try{return e.message=t+e.message,e}catch(t){return e}if(void 0===e)return new Error(t);try{return new Error(t+(0,D.P)(e))}catch(e){return new Error(t)}}(t.reason);(0,s.p)("err",[r,(0,p.z)(),!1,{unhandledPromiseRejection:1}],void 0,e.D.jserrors,this.ee)}),(0,O.m$)(!1,this.removeOnAbort?.signal)),(0,k.gy)(this.ee),(0,k.BV)(this.ee),(0,k.em)(this.ee),(0,t.OP)(r).xhrWrappable&&(0,k.Kf)(this.ee),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}onerrorHandler(t,r,n,i,o){"function"==typeof this.origOnerror&&this.origOnerror(...arguments);try{this.skipNext?this.skipNext-=1:(0,s.p)("err",[o||new F(t,r,n),(0,p.z)()],void 0,e.D.jserrors,this.ee)}catch(t){try{(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,this.ee)}catch(e){}}return!1}}function F(e,t,r){this.message=e||"Uncaught error with no additional information",this.sourceURL=t,this.line=r}let U=1;const q="nr@id";function G(e){const t=typeof e;return!e||"object"!==t&&"function"!==t?-1:e===c._A?0:(0,I.X)(e,q,(function(){return U++}))}function V(e){if("string"==typeof e&&e.length)return e.length;if("object"==typeof e){if("undefined"!=typeof ArrayBuffer&&e instanceof ArrayBuffer&&e.byteLength)return e.byteLength;if("undefined"!=typeof Blob&&e instanceof Blob&&e.size)return e.size;if(!("undefined"!=typeof FormData&&e instanceof FormData))try{return(0,D.P)(e).length}catch(e){return}}}var X=i(7243);class W{constructor(e){this.agentIdentifier=e,this.generateTracePayload=this.generateTracePayload.bind(this),this.shouldGenerateTrace=this.shouldGenerateTrace.bind(this)}generateTracePayload(e){if(!this.shouldGenerateTrace(e))return null;var r=(0,t.DL)(this.agentIdentifier);if(!r)return null;var n=(r.accountID||"").toString()||null,i=(r.agentID||"").toString()||null,o=(r.trustKey||"").toString()||null;if(!n||!i)return null;var a=(0,_.M)(),s=(0,_.Ht)(),c=Date.now(),u={spanId:a,traceId:s,timestamp:c};return(e.sameOrigin||this.isAllowedOrigin(e)&&this.useTraceContextHeadersForCors())&&(u.traceContextParentHeader=this.generateTraceContextParentHeader(a,s),u.traceContextStateHeader=this.generateTraceContextStateHeader(a,c,n,i,o)),(e.sameOrigin&&!this.excludeNewrelicHeader()||!e.sameOrigin&&this.isAllowedOrigin(e)&&this.useNewrelicHeaderForCors())&&(u.newrelicHeader=this.generateTraceHeader(a,s,c,n,i,o)),u}generateTraceContextParentHeader(e,t){return"00-"+t+"-"+e+"-01"}generateTraceContextStateHeader(e,t,r,n,i){return i+"@nr=0-1-"+r+"-"+n+"-"+e+"----"+t}generateTraceHeader(e,t,r,n,i,o){if(!("function"==typeof c._A?.btoa))return null;var a={v:[0,1],d:{ty:"Browser",ac:n,ap:i,id:e,tr:t,ti:r}};return o&&n!==o&&(a.d.tk=o),btoa((0,D.P)(a))}shouldGenerateTrace(e){return this.isDtEnabled()&&this.isAllowedOrigin(e)}isAllowedOrigin(e){var r=!1,n={};if((0,t.Mt)(this.agentIdentifier,"distributed_tracing")&&(n=(0,t.P_)(this.agentIdentifier).distributed_tracing),e.sameOrigin)r=!0;else if(n.allowed_origins instanceof Array)for(var i=0;i 2&&void 0!==arguments[2])||arguments[2];super(r,n,Z.t,i),(0,t.OP)(r).xhrWrappable&&(this.dt=new W(r),this.handler=(e,t,r,n)=>(0,s.p)(e,t,r,n,this.ee),(0,k.u5)(this.ee),(0,k.Kf)(this.ee),function(r,n,i,o){function a(e){var t=this;t.totalCbs=0,t.called=0,t.cbTime=0,t.end=E,t.ended=!1,t.xhrGuids={},t.lastSize=null,t.loadCaptureCalled=!1,t.params=this.params||{},t.metrics=this.metrics||{},e.addEventListener("load",(function(r){_(t,e)}),(0,O.m$)(!1)),c.IF||e.addEventListener("progress",(function(e){t.lastSize=e.loaded}),(0,O.m$)(!1))}function s(e){this.params={method:e[0]},T(this,e[1]),this.metrics={}}function u(e,n){var i=(0,t.DL)(r);i.xpid&&this.sameOrigin&&n.setRequestHeader("X-NewRelic-ID",i.xpid);var a=o.generateTracePayload(this.parsedOrigin);if(a){var s=!1;a.newrelicHeader&&(n.setRequestHeader("newrelic",a.newrelicHeader),s=!0),a.traceContextParentHeader&&(n.setRequestHeader("traceparent",a.traceContextParentHeader),a.traceContextStateHeader&&n.setRequestHeader("tracestate",a.traceContextStateHeader),s=!0),s&&(this.dt=a)}}function d(e,t){var r=this.metrics,i=e[0],o=this;if(r&&i){var a=V(i);a&&(r.txSize=a)}this.startTime=(0,p.z)(),this.listener=function(e){try{"abort"!==e.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==e.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof t.onload)&&"function"==typeof o.end)&&o.end(t)}catch(e){try{n.emit("internal-error",[e])}catch(e){}}};for(var s=0;s 1?e[1]=i:e.push(i)}else e[0]&&e[0].headers&&s(e[0].headers,n)&&(this.dt=n);function s(e,t){var r=!1;return t.newrelicHeader&&(e.set("newrelic",t.newrelicHeader),r=!0),t.traceContextParentHeader&&(e.set("traceparent",t.traceContextParentHeader),t.traceContextStateHeader&&e.set("tracestate",t.traceContextStateHeader),r=!0),r}}function x(e,t){this.params={},this.metrics={},this.startTime=(0,p.z)(),this.dt=t,e.length>=1&&(this.target=e[0]),e.length>=2&&(this.opts=e[1]);var r,n=this.opts||{},i=this.target;"string"==typeof i?r=i:"object"==typeof i&&i instanceof Y?r=i.url:c._A?.URL&&"object"==typeof i&&i instanceof URL&&(r=i.href),T(this,r);var o=(""+(i&&i instanceof Y&&i.method||n.method||"GET")).toUpperCase();this.params.method=o,this.txSize=V(n.body)||0}function A(t,r){var n;this.endTime=(0,p.z)(),this.params||(this.params={}),this.params.status=r?r.status:0,"string"==typeof this.rxSize&&this.rxSize.length>0&&(n=+this.rxSize);var o={txSize:this.txSize,rxSize:n,duration:(0,p.z)()-this.startTime};i("xhr",[this.params,o,this.startTime,this.endTime,"fetch"],this,e.D.ajax)}function E(t){var r=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(var o=0;o 2&&void 0!==arguments[2])||arguments[2];super(e,t,we.t,r),this.importAggregator()}}new class{constructor(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:(0,_.ky)(16);c._A?(this.agentIdentifier=t,this.sharedAggregator=new y({agentIdentifier:this.agentIdentifier}),this.features={},this.desiredFeatures=new Set(e.features||[]),this.desiredFeatures.add(m),Object.assign(this,(0,a.j)(this.agentIdentifier,e,e.loaderType||"agent")),this.start()):(0,l.Z)("Failed to initial the agent. Could not determine the runtime environment.")}get config(){return{info:(0,t.C5)(this.agentIdentifier),init:(0,t.P_)(this.agentIdentifier),loader_config:(0,t.DL)(this.agentIdentifier),runtime:(0,t.OP)(this.agentIdentifier)}}start(){const t="features";try{const r=n(this.agentIdentifier),i=[...this.desiredFeatures];i.sort(((t,r)=>e.p[t.featureName]-e.p[r.featureName])),i.forEach((t=>{if(r[t.featureName]||t.featureName===e.D.pageViewEvent){const n=function(t){switch(t){case e.D.ajax:return[e.D.jserrors];case e.D.sessionTrace:return[e.D.ajax,e.D.pageViewEvent];case e.D.sessionReplay:return[e.D.sessionTrace];case e.D.pageViewTiming:return[e.D.pageViewEvent];default:return[]}}(t.featureName);n.every((e=>r[e]))||(0,l.Z)("".concat(t.featureName," is enabled but one or more dependent features has been disabled (").concat((0,D.P)(n),"). This may cause unintended consequences or missing data...")),this.features[t.featureName]=new t(this.agentIdentifier,this.sharedAggregator)}})),(0,T.Qy)(this.agentIdentifier,this.features,t)}catch(e){(0,l.Z)("Failed to initialize all enabled instrument classes (agent aborted) -",e);for(const e in this.features)this.features[e].abortHandler?.();const r=(0,T.fP)();return delete r.initializedAgents[this.agentIdentifier]?.api,delete r.initializedAgents[this.agentIdentifier]?.[t],delete this.sharedAggregator,r.ee?.abort(),delete r.ee?.get(this.agentIdentifier),!1}}}({features:[J,m,S,class extends h{static featureName=oe;constructor(t,r){if(super(t,r,oe,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;const n=this.ee;let i;(0,k.QU)(n),this.eventsEE=(0,k.em)(n),this.eventsEE.on(se,(function(e,t){this.bstStart=(0,p.z)()})),this.eventsEE.on(ae,(function(t,r){(0,s.p)("bst",[t[0],r,this.bstStart,(0,p.z)()],void 0,e.D.sessionTrace,n)})),n.on(ce+ne,(function(e){this.time=(0,p.z)(),this.startPath=location.pathname+location.hash})),n.on(ce+ie,(function(t){(0,s.p)("bstHist",[location.pathname+location.hash,this.startPath,this.time],void 0,e.D.sessionTrace,n)}));try{i=new PerformanceObserver((t=>{const r=t.getEntries();(0,s.p)(te,[r],void 0,e.D.sessionTrace,n)})),i.observe({type:re,buffered:!0})}catch(e){}this.importAggregator({resourceObserver:i})}},C,xe,B,class extends h{static featureName=de;constructor(e,r){if(super(e,r,de,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;if(!(0,t.OP)(e).xhrWrappable)return;try{this.removeOnAbort=new AbortController}catch(e){}let n,i=0;const o=this.ee.get("tracer"),a=(0,k._L)(this.ee),s=(0,k.Lg)(this.ee),u=(0,k.BV)(this.ee),d=(0,k.Kf)(this.ee),f=this.ee.get("events"),l=(0,k.u5)(this.ee),h=(0,k.QU)(this.ee),g=(0,k.Gm)(this.ee);function m(e,t){h.emit("newURL",[""+window.location,t])}function v(){i++,n=window.location.hash,this[ve]=(0,p.z)()}function b(){i--,window.location.hash!==n&&m(0,!0);var e=(0,p.z)();this[pe]=~~this[pe]+e-this[ve],this[ye]=e}function y(e,t){e.on(t,(function(){this[t]=(0,p.z)()}))}this.ee.on(ve,v),s.on(be,v),a.on(be,v),this.ee.on(ye,b),s.on(ge,b),a.on(ge,b),this.ee.buffer([ve,ye,"xhr-resolved"],this.featureName),f.buffer([ve],this.featureName),u.buffer(["setTimeout"+le,"clearTimeout"+fe,ve],this.featureName),d.buffer([ve,"new-xhr","send-xhr"+fe],this.featureName),l.buffer([me+fe,me+"-done",me+he+fe,me+he+le],this.featureName),h.buffer(["newURL"],this.featureName),g.buffer([ve],this.featureName),s.buffer(["propagate",be,ge,"executor-err","resolve"+fe],this.featureName),o.buffer([ve,"no-"+ve],this.featureName),a.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"],this.featureName),y(l,me+fe),y(l,me+"-done"),y(a,"new-jsonp"),y(a,"jsonp-end"),y(a,"cb-start"),h.on("pushState-end",m),h.on("replaceState-end",m),window.addEventListener("hashchange",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("load",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("popstate",(function(){m(0,i>1)}),(0,O.m$)(!0,this.removeOnAbort?.signal)),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}],loaderType:"spa"})})(),window.NRBA=o})(); window.jQuery || document.write(' ') CKEDITOR_BASEPATH='https://f1000research.com/js/vendor/ckeditor/' window.reactTheme = 'research'; window.MathJax = { CommonHTML: { linebreaks: { automatic: true } }, 'HTML-CSS': { linebreaks: { automatic: true } }, SVG: { linebreaks: { automatic: true } }, AuthorInit: function() { MathJax.Hub.Register.MessageHook('End Process', function () { let timeout = false; // holder for timeout id const delay = 250; // delay after event is "complete" to run callback const reflowMath = function() { const dispFormulas = document.querySelectorAll('.disp-formula.panel'); if (!dispFormulas) { return; } for (const dispFormula of dispFormulas) { const child = dispFormula.querySelector('.MathJax_Preview').nextSibling.firstChild; const isMultiline = MathJax.Hub.getAllJax(dispFormula)[0].root.isMultiline; if (dispFormula.offsetWidth < child.offsetWidth || isMultiline) { MathJax.Hub.Queue(['Rerender', MathJax.Hub, dispFormula]); } } }; window.addEventListener('resize', function() { clearTimeout(timeout); // clear the timeout timeout = setTimeout(reflowMath, delay); // start timing for event "completion" }); }); }, }; if (window.location.hash == '#_=_'){ window.location = window.location.href.split('#')[0] } !function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function() {n.callMethod? n.callMethod.apply(n,arguments):n.queue.push(arguments)} ;if(!f._fbq)f._fbq=n; n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '1641728616063202'); fbq('track', "PixelInitialized", {}); (function(h,o,t,j,a,r){ h.hj=h.hj||function(){(h.hj.q=h.hj.q||[]).push(arguments)}; h._hjSettings={hjid:2318163,hjsv:6}; a=o.getElementsByTagName('head')[0]; r=o.createElement('script');r.async=1; r.src=t+h._hjSettings.hjid+j+h._hjSettings.hjsv; a.appendChild(r); })(window,document,'https://static.hotjar.com/c/hotjar-','.js?sv='); search file_upload Submit your research search menu close search Browse Gateways & Collections How to Publish Submit your Research My Submissions Article Guidelines Article Guidelines (New Versions) Open Data, Software and Code Guidelines Open Data and Accessible Source Materials Guidelines (HSS) Open Data, Software and Code Guidelines (PSE) Prepublication Checks Production Process Posters and Slides Guidelines Document Guidelines Article Processing Charges Peer Review Finding Article Reviewers About How it Works For Reviewers Our Advisors Policies Glossary FAQs For Developers Newsroom Contact My Research Submissions Content and Tracking Alerts My Details Sign In file_upload Submit your research { "@context": "https://schema.org", "@type": "ScholarlyArticle", "mainEntityOfPage": { "@type": "WebPage", "@id": "https://f1000research.com/articles/15-50" }, "headline": "THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL", "datePublished": "2026-01-13T11:34:28", "dateModified": "2026-04-15T05:03:09", "author": [ { "@type": "Person", "name": "Hülya Adıgüzel Okşar" }, { "@type": "Person", "name": "Adem Soydan" }, { "@type": "Person", "name": "Fatih Ulaş" }, { "@type": "Person", "name": "Semih Tek" }, { "@type": "Person", "name": "Metin Okşar" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": " Introductıon The aim of this study was to investigate the protective effects of apocynin in a selenite-induced cataract model, and to evaluate its impact on cataract severity and antioxidant enzyme activities. Methods Thirty-five rats were randomly separated into five groups (n = 7 per group). The control group received only saline. Groups 1, 2, 3, and 4 were administered sodium selenite at a dose of 30 nmol/g. In addition, Group 2 received dimethyl sulfoxide (DMSO), Group 3 received 10 mg/kg apocynin, and Group 4 received 20 mg/kg apocynin. The apocynin treatment was administered intraperitoneally for 7 consecutive days. Results Low-dose apocynin was seen to enhance antioxidant defence by increasing catalase (CAT) and glutathione reductase (GR) levels (p = 0.003, p = 0.002) without altering malondialdehyde (MDA) levels (p = 0.04). High-dose apocynin (20 mg/kg) led to an increase in MDA, suggesting a possible dose-related pro-oxidant effect. Conclusion This study suggests that apocynin, particularly at a low dose (10 mg/kg), may prevent selenite-induced cataract formation. Low-dose apocynin effectively delayed cataract progression by enhancing antioxidant defence and limiting oxidative stress. In contrast, high-dose exposure revealed a possible pro-oxidant effect, highlighting the need for careful dose optimization. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/15-50/v1", "name": "THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL" } } ] } Home Browse THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Adıgüzel Okşar H, Soydan A, Ulaş F et al. THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.12688/f1000research.174231.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] Hülya Adıgüzel Okşar https://orcid.org/0000-0002-5267-9743 1,2 , Adem Soydan 1 , Fatih Ulaş 1 , Semih Tek https://orcid.org/0000-0002-5353-8053 3 , Metin Okşar 1 Hülya Adıgüzel Okşar https://orcid.org/0000-0002-5267-9743 1,2 , Adem Soydan 1 , [...] Fatih Ulaş 1 , Semih Tek https://orcid.org/0000-0002-5353-8053 3 , Metin Okşar 1 PUBLISHED 13 Jan 2026 Author details Author details 1 Department of Ophtalmology, Bolu Abant Izzet Baysal University, Training and Research Hospital, Bolu, Turkey 2 Department of Ophthalmology, Evliya Celebi Training and Research Hospital, Kutahya, Turkey 3 Department of Biochemistry, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey Hülya Adıgüzel Okşar Roles: Conceptualization, Formal Analysis, Writing – Original Draft Preparation, Writing – Review & Editing Adem Soydan Roles: Writing – Review & Editing Fatih Ulaş Roles: Methodology, Writing – Review & Editing Semih Tek Roles: Software, Writing – Review & Editing Metin Okşar Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Eye Health gateway. Abstract Introductıon The aim of this study was to investigate the protective effects of apocynin in a selenite-induced cataract model, and to evaluate its impact on cataract severity and antioxidant enzyme activities. Methods Thirty-five rats were randomly separated into five groups (n = 7 per group). The control group received only saline. Groups 1, 2, 3, and 4 were administered sodium selenite at a dose of 30 nmol/g. In addition, Group 2 received dimethyl sulfoxide (DMSO), Group 3 received 10 mg/kg apocynin, and Group 4 received 20 mg/kg apocynin. The apocynin treatment was administered intraperitoneally for 7 consecutive days. Results Low-dose apocynin was seen to enhance antioxidant defence by increasing catalase (CAT) and glutathione reductase (GR) levels (p = 0.003, p = 0.002) without altering malondialdehyde (MDA) levels (p = 0.04). High-dose apocynin (20 mg/kg) led to an increase in MDA, suggesting a possible dose-related pro-oxidant effect. Conclusion This study suggests that apocynin, particularly at a low dose (10 mg/kg), may prevent selenite-induced cataract formation. Low-dose apocynin effectively delayed cataract progression by enhancing antioxidant defence and limiting oxidative stress. In contrast, high-dose exposure revealed a possible pro-oxidant effect, highlighting the need for careful dose optimization. READ ALL READ LESS Keywords Apocynin · Selenite · Cataract · Oxidative Stress Corresponding Author(s) Hülya Adıgüzel Okşar ( [email protected] ) Close Corresponding author: Hülya Adıgüzel Okşar Competing interests: No competing interests were disclosed. Grant information: This work was supported by the Republic of Turkey ABANT IZZET BAYSAL UNIVERSITY RECTORATE Scientific Research Projects Coordination Unit under Grant number [2021.08.13.1522.] The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2026 Adıgüzel Okşar H et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Adıgüzel Okşar H, Soydan A, Ulaş F et al. THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.12688/f1000research.174231.1 ) First published: 13 Jan 2026, 15 :50 ( https://doi.org/10.12688/f1000research.174231.1 ) Latest published: 15 Apr 2026, 15 :50 ( https://doi.org/10.12688/f1000research.174231.3 )  There is a newer version of this article available. Suppress this message for one day. Introduction Cataract, defined as the opacification of the lens, is the leading cause of reversible blindness, accounting for approximately 51% of all cases worldwide. 1 Although modern cataract surgery is generally regarded as highly safe and remains the only effective treatment for cataracts, it is not always accessible or affordable. Moreover, potential intraoperative and postoperative complications further highlight the need for non-surgical alternatives. 2 Oxidative stress is a major contributor to cataractogenesis, primarily through the imbalance between reactive oxygen species (ROS) and endogenous antioxidant defence systems such as CAT, superoxide dismutase (SOD), and glutathione peroxidase (GPx). 3 The accumulation of ROS promotes lipid peroxidation, protein aggregation, DNA damage, and apoptosis of lens epithelial cells, all of which contribute to lens opacification. 3 – 5 Recent metabolomic studies also indicate that cataract formation is accompanied by disruptions in glutathione-related pathways and other antioxidant-linked metabolites, further supporting the central role of oxidative imbalance in cataractogenesis. 6 Given its central role in cataract development, antioxidant therapy has been widely proposed as a promising non-surgical approach for delaying or preventing disease progression. 7 Various compounds, including sildenafil, melatonin, ascorbic acid, resveratrol, ellagic acid, N-acetylcysteine and rosmarinic acid have demonstrated protective effects in experimental cataract models. 2 , 4 , 8 – 12 Of these models used in previous research, the selenite-induced cataract model in rats is one of the most extensively utilized due to its reproducibility and close resemblance to age-related human cataracts. 2 , 4 Selenite administration disrupts calcium homeostasis, accelerates proteolysis, and depletes glutathione levels, thereby mimicking the molecular and structural alterations observed in human cataractogenesis. 2 , 13 Apocynin (4-hydroxy-3-methoxyacetophenone), a natural NADPH oxidase inhibitor derived from Picrorhiza kurroa and Apocynum cannabinum prevents the assembly of the NADPH oxidase complex and consequently reduces ROS production.apocynin has been Antioxidant, anti-inflammatory and cytoprotective effects have been reported in several systemic disease models. 14 Previous studies have demonstrated its beneficial roles in cardiovascular disease, renal injury, neuroinflammation, and metabolic disorders, largely attributed to its capacity to suppress oxidative stress and modulate redox-sensitive signaling pathways. 15 Furthermore, apocynin has been reported to enhance endogenous antioxidant defenses, preserve mitochondrial function, and attenuate inflammatory cytokine production in multiple in vivo models. 16 Despite these documented systemic benefits, its potential therapeutic effects in ocular tissues, particularly in cataract formation, remain insufficiently explored, highlighting the need for further investigation. The aim of this study was to investigate the potential protective effect of apocynin against selenite-induced cataract formation. In addition to assessing cataract severity, the impact on key oxidative stress biomarkers in the lens tissue was evaluated, including malondialdehyde (MDA), catalase (CAT), and glutathione reductase (GR). MDA is a well-established marker of lipid peroxidation and reflects structural damage caused by ROS, 17 whereas CAT and GR are critical enzymatic components of the endogenous antioxidant defence system. 18 These parameters were selected as they have been shown to be sensitive and relevant for the evaluation of redox imbalance in experimental cataract models. 19 An earlier version of this study was posted as a preprint. 20 Materials and Methods The establishment of the cataract rat model and other experimental procedures were conducted in the Experimental Animals Application and Research Centre of Abant Izzet Baysal University. Biochemical analyses were performed in the Biochemistry Laboratory of Basaksehir Cam and Sakura City Hospital. Prior to the study, ethical approval was obtained from the Animal Experiments Local Ethics Committee of Abant Izzet Baysal University (Date: 9 th June 2021, Approval Number: 2021/19). Experimental animals The study sample comprised a total of 35 healthy, male Sprague-Dawley rats, each weighing approximately 50 g on postnatal day 10, obtained from the Experimental Animals Research and Application Centre of Bolu Abant Izzet Baysal University. The experimental animals were kept in a laboratory room at a temperature of 20-24 °C and 40-60% humidity, with a 12 hr light-dark cycle. The rats had ad libitum access to standard feed and water, refreshed daily. All the rats were confirmed as having healthy eyes before starting the study. A selenite-induced cataract model was established in each rat on postnatal day 10 with a single dose (30 nmol/gr) subcutaneous injection of sodium selenite (Na2SeO3). In the literature, this model has been reported to usually manifest with the development of bilateral cataracts in rats within 16 days after eye opening. 2 The rats were separated into 5 groups of 7 animals. The Control group (n = 7) received only saline solution subcutaneously. Group 1 (n = 7) received 30 nmol/gr Na2SeO3 (Sigma Aldrich, Merck Group, USA, Cat. No: 214485-100G) subcutaneously. Group 2 (n = 7) received 30 nmol/gr Na2SeO3 subcutaneously and dimethyl sulphoxide (DMSO) (Sigma Aldrich, Merck Group, USA, Cat. No: 472301-500ML) intraperitoneally. Group 3 (n = 7) received 30 nmol/gr Na2SeO3 subcutaneously and 10 mg/kg apocynin (Sigma Aldrich, Merck Group, USA, Cat. No: 178385-1GM) intraperitoneally. Group 4 (n = 7) received 30 nmol/gr Na2SeO3 subcutaneously and 20 mg/kg apocynin intraperitoneally. The treatments (low- and high-dose apocynin) were administered daily for 7 consecutive days. Sodium selenite was dissolved in saline, and apocynin was dissolved in DMSO. No anaesthesia was administered to the rats during injections. Morphological examination of lens At the end of 14 days, the eyes of all the rats were dilated with 1% tropicamide (Tropamid Forte ® , Bilim Pharmaceuticals, Turkey). Ketalar ® (50 mg/kg) (Ketamin hydrochloride, Pfizer Pfe Medicines, Germany) and xylazinebio ® (10 mg/kg) (Xylazine, Bioveta, Czech Republic) were administered intramuscularly to induce anesthesia, and evisceration was performed. Euthanasia was then carried out by exsanguination after the surgery. The formation of cataract in each eye was examined under a biomicroscope (Topcon DC3 Japan) and the cataract was graded by coaxial illumination of an operating microscope (Zeiss Microsystem, Germany) using a seven-level grading system (0–6) ( Table 1 ) based on the extent and distribution of lens opacity: Table 1. Cataract grading scale. Degrees Microscopic findings in the lens 0 Normal transparent lens 1 First signs of nuclear opacity with small scatterings 2 Mild nuclear opacity 3 Diffuse nuclear opacity with cortical scattering 4 Partial nuclear opacity 5 Distinct nuclear opacity 6 Mature cataract in the whole lens Grade 0: Normal transparent lens Grade 1: First signs of nuclear opacity with small scatterings Grade 2: Mild nuclear opacity Grade 3: Diffuse nuclear opacity accompanied by cortical scattering Grade 4: Partial nuclear opacity Grade 5: Distinct nuclear opacity Grade 6: Mature cataract involving the entire lens Magnification and illumination settings were kept constant for all examinations, and both direct and retroillumination views were obtained. Each lens was evaluated twice; in case of disagreement >1 grade, a third evaluation would be performed. To minimize bias, the order of animal assessment was randomized, and all observations were conducted by a single investigator blinded to group allocations. Biochemical analyses The removed lens tissues were placed in liquid nitrogen and stored at -80°C for one week until the analysis. The rat lens tissues were sent to the Biochemistry Laboratory of the Department of Medical Microbiology, Basaksehir Cam and Sakura City Hospital, and the levels of malondialdehyde (MDA), glutathione reductase (GR), and catalase (CAT) were measured using the enzyme-linked immunosorbent assay (ELISA) method. Tissues were weighed and then homogenized in phosphate buffer solution (PBS; pH 7.4) [tissue weight (g): PBS (ml) volume = 1:9] on ice to prevent overheating. After homogenization, the samples were centrifuged at 5000 g for 5 min. MDA levels were measured using a Rat MDA ELISA kit (BT Lab, China), catalase levels were measured with a Rat CAT ELISA kit (BT Lab, China) and glutathione reductase levels with a Rat GR ELISA kit (BT Lab, China) using the colorimetric sandwich solid-phase enzyme-immunoassay method. Statistical analyses SPSS version 25.0 software (IBM Corporation, Armonk, NY, USA) was used to analyze the data collected from this experimental study. The descriptive data of cataract grades and biochemical parameters measured in lens tissues were presented as mean and standard deviation (minimum and maximum) values. The distribution of the data was tested using the Kolmogorov-Smirnov test. Comparisons of variables between groups were performed using One-way ANOVA. The Tukey Kramer Multiple Comparison test was applied in post-hoc analyses. The Mann-Whitney U test was used for pairwise comparisons. A value of p < 0.05 was accepted as statistically significant. Results Morphological examination of cataract formation The microscopic images obtained from the rat lenses are presented shown in Figure 1 , and the clinical assessment results regarding cataract grading are summarized shown in Table 2 . Cataract formation was observed in all rats in Group 1, confirming the success of the selenite-induced cataract model used in this experimental study. Figure 1. Right and left microscopic images of lenses obtained from rats with cataract. Table 2. The cataract grades of lenses in the experimental cataract model. NUMBER of LENSES CONTROL GROUP 1 GROUP 2 GROUP 3 GROUP 4 1 0 6 5 1 2 2 0 5 5 1 2 3 0 5 4 2 3 4 0 6 5 1 3 5 0 6 4 1 2 6 0 5 4 2 4 7 0 6 4 2 2 8 0 5 4 2 4 9 0 5 5 1 2 10 0 5 4 1 2 11 0 5 4 2 3 12 0 6 5 1 4 13 0 6 5 1 2 14 0 5 4 2 2 X ± SS 0 ± 0 5.40 ± 0.52 4.40 ± 0.52 1.4 ± 0.52 *** 2.60 ± 0.84 * Min-Max 0 – 0 5 – 6 4 – 5 1 – 2 2 – 4 *** p < 0.001 and * p < 0.05 : Compared with the control group. Slit-lamp biomicroscopic evaluation revealed that sodium selenite administration resulted in marked lens opacities in Groups 1 and 2, whereas apocynin treatment significantly reduced cataract severity (p < 0.001, p < 0.05). The low-dose apocynin group (Group 3) had much lower cataract grades compared to the high-dose group (Group 4). The detailed cataract grading of all the groups is shown in Table 2 . Biochemical analyses of lenses In the selenite (Group 1) and DMSO (Group 2) groups, MDA levels were significantly elevated compared to the control group (p < 0.001). No significant change in MDA levels was observed in Group 3 (p = 0.99), and Group 4 showed a significant increase in MDA levels (p = 0.04). This finding suggests a potential pro-oxidant effect at the higher dose of apocynin (shown in Figure 2 and Table 3 ). Figure 2. Box-plot graph presentation of comparison of malondialdehyde (MDA) levels measured in lenses between the experimental groups. *p < 0.05, **p < 0.01 and ***p < 0.001 vs the control group. Table 3. Comparison of biochemical parameters measured in lenses in the experimental cataract model. Biochemical parameter Control Group 1 Group 2 Group 3 Group 4 P value MDA (nmol/ml) 0.57 ± 0.05 0.88 ± 0.09 0.80 ± 0.18 0.84 ± 0.07 1.07 ± 0.06 <0.0001 0.49 – 0.62 0.79 – 0.99 0.62 – 1.09 0.74 – 0.92 1.00 – 1.15 Catalase (ng/ml) 64.94 ± 3.46 29.56 ± 11.66 41.99 ± 16.31 57.44 ± 6.71 44.79 ± 6.76 0.0002 59.88-68.33 20.47 – 49.77 25.53 – 64.79 46.51 – 63.72 36.63 – 53.49 GR (ng/ml) 18.88 ± 2.73 11.12 ± 2.41 13.31 ± 2.49 18.01 ± 2.51 20.61 ± 2.54 <0.0001 15.52–21.33 7.78 – 13.87 9.91 – 16.86 15.37 – 20.87 17.26 – 23.14 CAT activity was significantly reduced in the selenite and DMSO groups (Groups 1 and 2) (p 0.05) (Shown in Figure 3 and Table 3 ). Figure 3. Box-plot graph presentation of comparison of catalase levels measured in lenses between the experimental groups. *p < 0.05 and ***p < 0.001 vs the control group. GR levels were significantly decreased in the selenite group. A statistically significant increase in GR activity was observed in both Group 3 and Group 4 (p < 0.05) (shown in Figure 4 and Table 3 ). Figure 4. Box-plot graph presentation of comparison of glutathione reductase (GR) levels measured in lenses between the experimental groups. *p < 0.05 and **p < 0.01 vs the control group. Discussion The results of this study demonstrated that apocynin, particularly at a low dose (10 mg/kg), exerted protective effects against selenite-induced cataractogenesis in rats. These effects were supported by reduced lens opacification and restoration of antioxidant enzyme activities. Low-dose apocynin significantly increased catalase (CAT) and glutathione reductase (GR) activities to levels comparable with those of the control group. Moreover, the oxidative stress marker malondialdehyde (MDA) did not increase and remained similar to control levels, indicating effective prevention of lipid peroxidation. Oxidative stress plays a central role in cataract pathogenesis. The selenite-induced cataract model is widely used due to its rapid onset, simplicity, reproducibility, and strong resemblance to human age-related cataracts, particularly in terms of glutathione depletion, lipid peroxidation, and insoluble lens protein accumulation. 2 , 4 , 13 In the current study, the model validity was confirmed by the development of dense nuclear opacities in Group 1, together with elevated MDA levels and reduced CAT and GR activities, indicating oxidative stress. Despite inducing a partial enhancement in antioxidant enzyme activities (demonstrated by selective enhancement of GR activity, with minimal influence on CAT levels), high-dose apocynin (20 mg/kg) was found to increase MDA levels. This paradox suggests that the antioxidant benefits of apocynin may be counteracted by dose-dependent toxicity, resulting in a pro-oxidant response. This interpretation is consistent with literature indicating that excessive suppression of physiological ROS signaling can disrupt cellular homeostasis. 21 , 22 Similar dual effects have been reported for other redox-active compounds such as resveratrol and quercetin, which show cytoprotective effects at low doses but may induce oxidative stress, DNA damage, and apoptosis at higher concentrations. 23 , 24 Similar antioxidant protection has also been demonstrated for curcumin in rabbit cataract models, where curcumin reduced oxidative stress and delayed lens opacification. 25 Although curcumin and apocynin act through different upstream pathways, both compounds converge on modulating oxidative damage, supporting the broader relevance of redox-targeted therapeutic strategies in cataract prevention. In addition, the potential contribution of DMSO as a vehicle to these effects should not be overlooked, as it has been shown to exert cytotoxic and pro-oxidant effects under certain conditions. 26 The findings of this study highlight the importance of carefully optimizing both the dose and duration when evaluating antioxidant compounds in preclinical studies. Additionally highlight the need for careful dose optimization in human applications, as dose-dependent shifts between antioxidant and pro-oxidant activity may also occur in clinical settings. The production of NADPH oxidase–driven reactive oxygen species (ROS) production plays a critical role in cataractogenesis by promoting protein aggregation, lipid peroxidation, and lens opacification. 27 Given that oxidative stress is a key mechanism in selenite-induced cataract formation, 4 , 9 targeting ROS-generating pathways has therapeutic relevance. Therefore, apocynin, which is an inhibitor of NADPH oxidase, was selected for its potential to suppress intracellular ROS production and enhance endogenous antioxidant defence systems, including catalase and glutathione reductase. 28 , 29 Consistent with previous reports of oxidative stress-related disease models the current study results demonstrate that apocynin exerts protective effects on lens tissue, most likely through both antioxidant and anti-inflammatory mechanism. 28 – 30 In line with earlier findings in studies of retinal injury and diabetic retinopathy, 31 , 32 apocynin treatment was found to reduce cataract severity and modulate oxidative biomarkers in the current study model. Importantly, this study is among the first to have compared different apocynin doses in a cataract model. The findings indicate that low-dose apocynin is more effective than a high dose in reducing oxidative damage, thereby emphasizing the importance of dose optimization to achieve therapeutic benefit while minimizing toxicity. The biochemical analysis results further support these outcomes. Elevated malondialdehyde (MDA) levels in the selenite group confirmed increased lipid peroxidation, while apocynin treatment, particularly at low doses, reduced MDA levels. Similarly, catalase and glutathione reductase (GR) activities were preserved or enhanced with apocynin, indicating improved redox balance. As disruption of antioxidant enzymes is associated with lens protein denaturation and cataract progression, 33 , 34 the ability of apocynin to stabilize these enzymes may underlie its protective mechanism. The results of this study also support a strategic approach for the non-surgical prevention of cataract. Although cataract surgery remains the most effective treatment, access to surgical care is limited in many low- and middle-income countries due to resource constraints and economic burden. 35 , 36 Pharmacological interventions based on natural compounds may offer a safe, cost-effective, and preventive alternative for early-stage cataracts. Given its pharmacokinetic profile and pleiotropic effects, apocynin emerges as a strong candidate for further preclinical and clinical investigations. Unlike other antioxidant agents such as ascorbic acid, resveratrol, melatonin, ellagic acid, N-acetylcysteine, rosmarinic acid, and sildenafil, apocynin directly targets the NADPH oxidase complex, a key enzymatic source of ROS generation, offering a more upstream and specific modulation of oxidative stress. 14 This unique mechanism may confer broader and more sustained protective effects in lens tissue. This study had several limitations that should be acknowledged. First, although the results suggest beneficial effects of apocynin, there was no assessment of the molecular mechanisms underlying its modulation of redox signaling in the lens. Key antioxidant pathways such as Nrf2/ARE, thioredoxin, and glutaredoxin systems, as well as apoptotic markers, were not evaluated. 21 A second limitation was that the biochemical analysis was limited to ELISA-based measurements, and more detailed molecular techniques such as Western blotting or RT-PCR were not performed. In addition, apocynin was administered exclusively via the intraperitoneal route. Therefore, the comparative efficacy of alternative delivery methods, such as oral, topical, or intravitreal administration, remains unknown. The treatment duration was short-term, and the effects of long-term administration were not investigated. Finally, the absence of a positive control group using a well-characterized antioxidant agent limits the broader interpretability and comparability of the findings. Conclusion The results of this study demonstrated that apocynin, particularly at a low dose (10 mg/kg), exerts a significant protective effect against selenite-induced cataract formation in a rat model. This beneficial outcome is believed to be mediated through the enhancement of endogenous antioxidant defence mechanisms in the lens, as evidenced by increased catalase and glutathione reductase activities and the absence of elevated MDA levels. In contrast, high-dose apocynin (20 mg/kg) was associated with increased lipid peroxidation, suggesting a potential dose-dependent pro-oxidant effect. These findings emphasize the importance of dose optimization in the therapeutic application of antioxidant compounds. Although the results are promising, they remain preliminary and require further validation through comprehensive histopathological and molecular studies. If confirmed by future research, apocynin may be considered a novel pharmacological agent for preventing or delaying cataractogenesis through modulation of redox signaling in the lens. Statement of ethics The procedures applied to all animals involved in the study comply with the standards outlined in the Universal Declaration of Animal Rights, proclaimed at UNESCO in Paris in 1978. Prior to the study, ethical approval was obtained from the Animal Experiments Local Ethics Committee of Abant Izzet Baysal University (Date: 9th June 2021, Approval Number: 2021/19). Data availability statement Underlying data Repository name: Zenodo: Underlying data for “The Protective Effect of Apocynin on a Selenite-Induced Cataract Model”. https://doi.org/10.5281/zenodo.17952325 . 37 The project contains the following underlying data: Lens_opacity_scores.xlsx (individual lens opacity grading scores for all experimental animals). Biochemical_measurements.xlsx (raw biochemical data including MDA, CAT, and GR levels). Extended data Repository name: Zenodo: ARRIVE 2.0 checklist for “The Protective Effect of Apocynin on a Selenite-Induced Cataract Model”. https://doi.org/10.5281/zenodo.18048822 . 38 This project contains the following extended data: ARRIVE_2.0_Full_Checklist.docx (fully completed ARRIVE 2.0 author checklist). Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication) . Acknowledgments The authors thank the staff of the Experimental Animals Laboratory of Abant Izzet Baysal University for their technical assistance and support during the study. References 1. Lim JC, Arredondo MC, Braakhuis AJ, et al. : Vitamin C and the lens: new insights into delaying the onset of cataract. Nutrients. 2020; 12 (10): 3142. PubMed Abstract | Publisher Full Text | Free Full Text 2. Atalay HT, Ucgul AY, Turkcu UO, et al. : The effect of sildenafil on selenite-induced cataract in rats. Curr. Eye Res. 2020; 45 (9): 1082–1088. PubMed Abstract | Publisher Full Text 3. Vinson JA: Oxidative stress in cataracts. Pathophysiology. 2006; 13 (3): 151–162. Publisher Full Text 4. Yağci R, et al. : Use of Melatonin to Prevent Selenite-Induced Cataract Formation in Rat Eyes. Curr. Eye Res. 2006; 31 (10): 845–850. PubMed Abstract | Publisher Full Text 5. Tewari D, Samoilă O, Gocan D, et al. : Medicinal plants and natural products used in cataract management. Front. Pharmacol. 2019; 10 : 466. PubMed Abstract | Publisher Full Text | Free Full Text 6. Zemītis A, Stalidzāne L, Ustinova A, et al. : Metabolomic disparities in intraocular fluid across varied stages of cataract progression: implications for the analysis of cataract development. J. Ocul. Pharmacol. Ther. 2024; 40 (8): 477–485. PubMed Abstract | Publisher Full Text 7. Wang L, Li X, Men X, et al. : Research progress on antioxidants and protein aggregation inhibitors in cataract prevention and therapy. Mol. Med. Rep. 2024; 31 (1): 22. PubMed Abstract | Publisher Full Text | Free Full Text 8. Varma SD, Richards RD: (1988) Ascorbic acid and the eye lens. Ophthalmic Res. 1988; 20 (3): 164–173. Publisher Full Text 9. Doganay S, Borazan M, Iraz M, et al. : The effect of resveratrol in experimental cataract model formed by sodium selenite. Curr. Eye Res. 2006; 31 (2): 147–153. PubMed Abstract | Publisher Full Text 10. Sakthivel M, et al. : Prevention of selenite-induced cataractogenesis in Wistar rats by the polyphenol, ellagic acid. Exp. Eye Res. 2008; 86 (2): 251–259. PubMed Abstract | Publisher Full Text 11. Aydin B, et al. : Prevention of selenite-induced cataractogenesis by N-acetylcysteine in rats. Curr. Eye Res. 2009; 34 (3): 196–201. PubMed Abstract | Publisher Full Text 12. Tsai CF, Wu JY, Hsu YW: Protective effects of rosmarinic acid against selenite-induced cataract and oxidative damage in rats. Int. J. Med. Sci. 2019; 16 (5): 729–740. PubMed Abstract | Publisher Full Text | Free Full Text 13. Turgut B, Ergen İ, İlhan N: The protective effect of sesamol in the selenite-induced experimental cataract model. Turk. J. Ophthalmol. 2017; 47 (6): 309–314. PubMed Abstract | Publisher Full Text | Free Full Text 14. Boshtam M, Kouhpayeh S, Amini F, et al. : Anti-inflammatory effects of apocynin: a narrative review of the evidence. All Life. 2021; 14 (1): 997–1010. Publisher Full Text 15. Simonyi A, Serfozo P, Lehmidi TM, et al. : The neuroprotective effects of apocynin. Front. Biosci. (Elite Ed.). 2012; E4 : 2183–2193. PubMed Abstract | Publisher Full Text | Free Full Text 16. ’t Hart BA, Copray S, Philippens I: Apocynin, a low molecular oral treatment for neurodegenerative disease. Biomed. Res. Int. 2014; 2014 : 298020. PubMed Abstract | Publisher Full Text | Free Full Text 17. Lee BJ, Afshari NA, Shaw PX: Oxidative stress and antioxidants in cataract development. Curr. Opin. Ophthalmol. 2024; 35 (1): 57–63. Publisher Full Text 18. Ighodaro OM, Akınloye OA: First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex. J. Med. 2018; 54 (4): 287–293. Publisher Full Text 19. Li J, Buonfiglio F, Zeng Y, et al. : Oxidative Stress in Cataract Formation: Is There a Treatment Approach on the Horizon? Antioxidants (Basel). 2024; 13 (10): 1249. PubMed Abstract | Publisher Full Text | Free Full Text 20. Oksar HA, Soydan A, Ulaş F, et al. : The Protective Effect of Apocynin on a Selenite-Induced Cataract Model. Research Square. 2025. Preprint. Publisher Full Text 21. Trevelin SC, Santos L, Borges VF, et al. : Apocynin and Nox2 regulate NF-κB by modifying thioredoxin-1 redox-state. Sci. Rep. 2016; 6 (1): 34581. PubMed Abstract | Publisher Full Text | Free Full Text 22. Kozlov AV, Javadov S, Sommer N: Cellular ROS and antioxidants: physiological and pathological role. Antioxidants. 2024; 13 (5): 602. PubMed Abstract | Publisher Full Text | Free Full Text 23. Galiniak S, Aebisher D, Bartusik-Aebisher D: Potential Adverse Effects of Resveratrol: A Literature Review. Int. J. Mol. Sci. 2020; 21 (6): 2084. PubMed Abstract | Publisher Full Text | Free Full Text 24. Boots AW, Haenen GRMM, Bast A: Health effects of quercetin: From antioxidant to nutraceutical. Eur. J. Pharmacol. 2008; 585 (2–3): 325–337. Publisher Full Text 25. Hassan OA, Abu-raghif AR, Ridha-Salman H, et al. : Anti-cataractogenic impact of Curcuma longa extract eye drops on a rabbit model of sodium selenite–induced oxidative injury. Nutrire. 2025; 50 (2): 1–14. Publisher Full Text 26. Costa LA, Ottoni MHF, dos Santos MG , et al. : Dimethyl sulfoxide (DMSO) decreases cell proliferation and TNF-α, IFN-γ, and IL-2 cytokines production in cultures of peripheral blood lymphocytes. Molecules. 2017; 22 (11): 1789. PubMed Abstract | Publisher Full Text | Free Full Text 27. Das SJ, Wishart TFL, Jandeleit-Dahm K, et al. : Nox4-mediated ROS production is involved, but not essential for TGFβ-induced lens epithelial–mesenchymal transition leading to cataract. Exp. Eye Res. 2020; 192 : 107918. Publisher Full Text 28. Kouki A, Ferjani W, Ghanem-Boughanmi N, et al. : The NADPH oxidase inhibitors apocynin and diphenyleneiodonium protect rats from LPS-induced pulmonary inflammation. Antioxidants (Basel). 2023; 12 (3): 770. PubMed Abstract | Publisher Full Text | Free Full Text 29. Teuber JP, Essandoh K, Hummel SL, et al. : NADPH oxidases in diastolic dysfunction and heart failure with preserved ejection fraction. Antioxidants. 2022; 11 (9): 1822. PubMed Abstract | Publisher Full Text | Free Full Text 30. Furukawa T, Kurosawa T, Mifune Y, et al. : Elicitation of inhibitory effects for AGE-induced oxidative stress in rotator cuff-derived cells by apocynin. Curr. Issues Mol. Biol. 2023; 45 (4): 3434–3445. PubMed Abstract | Publisher Full Text | Free Full Text 31. Ahmad A, Nawaz MI, Siddiquei MM, et al. : Apocynin ameliorates NADPH oxidase 4 (NOX4)-induced oxidative damage in hypoxic human retinal Müller cells and diabetic rat retina. Mol. Cell. Biochem. 2021; 476 (5): 2099–2109. PubMed Abstract | Publisher Full Text 32. Wang H, Han X, Wittchen ES, et al. : TNF-α mediates choroidal neovascularization by upregulating VEGF expression in RPE through ROS-dependent β-catenin activation. Mol. Vis. 2016; 22 : 116–128. PubMed Abstract | Publisher Full Text | Free Full Text 33. Kulbay M, Wu KY, Nirwal GK, et al. : Oxidative stress and cataract formation: evaluating the efficacy of antioxidant therapies. Biomolecules. 2024; 14 (9): 1055. PubMed Abstract | Publisher Full Text | Free Full Text 34. Atalay E, Oğurel T, Derici MK: The role of oxidative damage in cataract etiopathogenesis. Therapeutic Advances in Ophthalmology. 2023; 5 : 25158414231168813. Publisher Full Text 35. Flessa S, Moeller M, Ensor T, et al. : Cataract surgery in low-income countries: a good deal!. Healthcare (Basel). 2022; 10 (12): 2580. PubMed Abstract | Publisher Full Text | Free Full Text 36. Lansingh VC, Carter MJ: Use of global visual acuity data in a time trade-off approach to calculate the cost utility of cataract surgery. Arch. Ophthalmol. 2009; 127 (9): 1183–1193. PubMed Abstract | Publisher Full Text 37. Oksar HA, Soydan A, Ulaş F, et al. : ARRIVE Checklist for: The Protective Effect of Apocynin on a Selenite-Induced Cataract Model. Zenodo. 2025. Publisher Full Text 38. Oksar HA, Soydan A, Ulaş F, et al. : Underlying dataset for: The Protective Effect of Apocynin on a Selenite-Induced Cataract Model. Zenodo. 2025. Publisher Full Text Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 13 Jan 2026 ADD YOUR COMMENT Comment Author details Author details 1 Department of Ophtalmology, Bolu Abant Izzet Baysal University, Training and Research Hospital, Bolu, Turkey 2 Department of Ophthalmology, Evliya Celebi Training and Research Hospital, Kutahya, Turkey 3 Department of Biochemistry, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey Hülya Adıgüzel Okşar Roles: Conceptualization, Formal Analysis, Writing – Original Draft Preparation, Writing – Review & Editing Adem Soydan Roles: Writing – Review & Editing Fatih Ulaş Roles: Methodology, Writing – Review & Editing Semih Tek Roles: Software, Writing – Review & Editing Metin Okşar Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information This work was supported by the Republic of Turkey ABANT IZZET BAYSAL UNIVERSITY RECTORATE Scientific Research Projects Coordination Unit under Grant number [2021.08.13.1522.] The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (3) version 3 Revised Published: 15 Apr 2026, 15:50 https://doi.org/10.12688/f1000research.174231.3 version 2 Revised Published: 14 Feb 2026, 15:50 https://doi.org/10.12688/f1000research.174231.2 version 1 Published: 13 Jan 2026, 15:50 https://doi.org/10.12688/f1000research.174231.1 Copyright © 2026 Adıgüzel Okşar H et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Adıgüzel Okşar H, Soydan A, Ulaş F et al. THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.12688/f1000research.174231.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 13 Jan 2026 Views 0 Cite How to cite this report: Choudhary R. Reviewer Report For: THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.5256/f1000research.192115.r450308 ) The direct URL for this report is: https://f1000research.com/articles/15-50/v1#referee-response-450308 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 06 Feb 2026 Rajesh Choudhary , Shri Shankaracharya Professional University, Chhattisgarh, Chhattisgarh, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.192115.r450308 Authors explore the protective effects of apocynin on cataract formation. The authors well explained the research background and concluded the research with their results. During the statistical analysis, why was the data of the apocynin-treated group (Group III and IV) ... Continue reading READ ALL Authors explore the protective effects of apocynin on cataract formation. The authors well explained the research background and concluded the research with their results. During the statistical analysis, why was the data of the apocynin-treated group (Group III and IV) were not compared with Group I or II in results table or figure. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Diabetes, Cataract I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Choudhary R. Reviewer Report For: THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.5256/f1000research.192115.r450308 ) The direct URL for this report is: https://f1000research.com/articles/15-50/v1#referee-response-450308 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 14 Feb 2026 Hülya adıgüzel okşar , Department of Ophtalmology, Bolu Abant Izzet Baysal University, Training and Research Hospital, Bolu, Turkey 14 Feb 2026 Author Response We thank the reviewer for the positive and constructive evaluation of our manuscript. Regarding the statistical analysis, we would like to clarify that following statistically significant overall group differences, post-hoc ... Continue reading We thank the reviewer for the positive and constructive evaluation of our manuscript. Regarding the statistical analysis, we would like to clarify that following statistically significant overall group differences, post-hoc pairwise comparisons were performed as specified in the Methods section. In these analyses, apocynin-treated groups (Groups III and IV) were compared with both the selenite-only group (Group I) and the DMSO group (Group II). These comparisons demonstrated that apocynin-treated groups exhibited significantly more favorable oxidative stress profiles and reduced cataract severity. To improve clarity and transparency, we have now explicitly stated this in the Results section. We appreciate the reviewer’s careful assessment of the statistical interpretation and thank them for their overall positive evaluation of the study. We thank the reviewer for the positive and constructive evaluation of our manuscript. Regarding the statistical analysis, we would like to clarify that following statistically significant overall group differences, post-hoc pairwise comparisons were performed as specified in the Methods section. In these analyses, apocynin-treated groups (Groups III and IV) were compared with both the selenite-only group (Group I) and the DMSO group (Group II). These comparisons demonstrated that apocynin-treated groups exhibited significantly more favorable oxidative stress profiles and reduced cataract severity. To improve clarity and transparency, we have now explicitly stated this in the Results section. We appreciate the reviewer’s careful assessment of the statistical interpretation and thank them for their overall positive evaluation of the study. Competing Interests: The authors declare that they have no competing interests. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 14 Feb 2026 Hülya adıgüzel okşar , Department of Ophtalmology, Bolu Abant Izzet Baysal University, Training and Research Hospital, Bolu, Turkey 14 Feb 2026 Author Response We thank the reviewer for the positive and constructive evaluation of our manuscript. Regarding the statistical analysis, we would like to clarify that following statistically significant overall group differences, post-hoc ... Continue reading We thank the reviewer for the positive and constructive evaluation of our manuscript. Regarding the statistical analysis, we would like to clarify that following statistically significant overall group differences, post-hoc pairwise comparisons were performed as specified in the Methods section. In these analyses, apocynin-treated groups (Groups III and IV) were compared with both the selenite-only group (Group I) and the DMSO group (Group II). These comparisons demonstrated that apocynin-treated groups exhibited significantly more favorable oxidative stress profiles and reduced cataract severity. To improve clarity and transparency, we have now explicitly stated this in the Results section. We appreciate the reviewer’s careful assessment of the statistical interpretation and thank them for their overall positive evaluation of the study. We thank the reviewer for the positive and constructive evaluation of our manuscript. Regarding the statistical analysis, we would like to clarify that following statistically significant overall group differences, post-hoc pairwise comparisons were performed as specified in the Methods section. In these analyses, apocynin-treated groups (Groups III and IV) were compared with both the selenite-only group (Group I) and the DMSO group (Group II). These comparisons demonstrated that apocynin-treated groups exhibited significantly more favorable oxidative stress profiles and reduced cataract severity. To improve clarity and transparency, we have now explicitly stated this in the Results section. We appreciate the reviewer’s careful assessment of the statistical interpretation and thank them for their overall positive evaluation of the study. Competing Interests: The authors declare that they have no competing interests. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Widyawati S. Reviewer Report For: THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.5256/f1000research.192115.r451976 ) The direct URL for this report is: https://f1000research.com/articles/15-50/v1#referee-response-451976 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 06 Feb 2026 Syska Widyawati , University of Indonesia, Jakarta, Indonesia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.192115.r451976 1. Title and Abstract Strengths The title accurately reflects the topic and research model The abstract summarizes objectives, interventions, and principal outcomes. Concerns Randomization ... Continue reading READ ALL 1. Title and Abstract Strengths The title accurately reflects the topic and research model The abstract summarizes objectives, interventions, and principal outcomes. Concerns Randomization is stated but not explicitly highlighted in the abstract and the title The introduction of the abstract currently states only the aim of the study without providing sufficient context regarding the scientific or clinical importance of the research Primary versus secondary outcomes are not clearly distinguished in the abstract 2. Introduction Strengths Well-structured background with appropriate citation of oxidative stress in cataractogenesis, with a clear identification of a knowledge gap regarding apocynin in lens tissue. Concerns The hypothesis is implied rather than explicitly stated. The citation about the magnitude of cataract problems cited from other study that were not epidemiology of cataract. For claims related to the prevalence of cataract, its contribution to global blindness, or its public health burden, the authors should cite authoritative epidemiological sources, such as population-based studies, systematic reviews, or global burden analyses (e.g., WHO or Global Burden of Disease reports). 3. Methods 3.1 Trial Design Strengths Ethical clearance mentioned clear description and uniformity of the experimental animals. The use of age-matched, sex-matched Sprague–Dawley rats with a clearly defined postnatal age and body weight enhances internal validity and reduces biological variability that could confound oxidative stress–related outcomes Doses, routes, duration, and vehicles are clearly specified. The biochemical analyses are clearly described and based on well-established, standardized methods. Concerns While the study includes multiple experimental groups, the manuscript does not sufficiently justify the rationale for including each group or clearly explain the specific purpose of each treatment arm within the study design No schematic timeline of interventions and assessments. The study is randomized but the method is insufficiently detailed. Justification for sample size (n=7 per group) is absent or sample size calculation preferred No pharmacokinetic rationale for selected apocynin doses The morphological evaluation of lens opacity relies on a grading system developed by the authors and assessed by a single examiner. Although the examiner was reported to be blinded to group allocation, this approach remains inherently subjective and may introduce observer-related bias, particularly because cataract grade is a key comparative outcome between experimental groups Results Strengths Clear presentation of cataract grades and biochemical data. Figures are generally interpretable and consistent with tables. Dose-dependent divergence between antioxidant and pro-oxidant effects is convincingly shown. The table already provides mean ± SD and min–max values, which sufficiently describe central tendency and dispersion for the reported comparisons. Concerns Table 2 formatting is confusing and appears duplicated. Cataract grading scales are inherently ordinal, reflecting increasing severity categories rather than equal-interval continuous measurements. As such, the use of means assumes equal distance between grades, which may not accurately reflect the biological or optical progression of lens opacity. This approach may therefore introduce bias and potentially overstate precision when comparing groups Two lenses from one rat are not independent (shared genetics, environment, exposure). Treating them as independent inflates sample size and can make p-values artificially small (pseudo-replication) Without additional emphasis on distributional features (e.g., skewness or outliers), the boxplots appear largely redundant rather than complementary. A statistically significant omnibus (multivariate or overall) test should be followed by clearly defined and consistently reported post-hoc pairwise comparisons to determine where the differences lie Discussion Strengths Thoughtful interpretation of dose-dependent redox effects. Integration with broader antioxidant literature is appropriate. Limitations are openly acknowledged. Key Scientific Limitation Lack of mechanistic validation (e.g., NADPH oxidase activity, Nrf2 signaling). Stating that apocynin inhibits NADPH oxidase does not fully explain how this mechanism translates into superior or more upstream protection compared with conventional antioxidants that primarily act as reactive oxygen species scavengers. If the authors wish to argue that apocynin is more effective than other antioxidant agents previously tested in cataract models, a clearer mechanistic framework is required Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: cornea cataract and refractive surgery I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Widyawati S. Reviewer Report For: THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.5256/f1000research.192115.r451976 ) The direct URL for this report is: https://f1000research.com/articles/15-50/v1#referee-response-451976 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 14 Feb 2026 Hülya adıgüzel okşar , Department of Ophtalmology, Bolu Abant Izzet Baysal University, Training and Research Hospital, Bolu, Turkey 14 Feb 2026 Author Response 1.Title and Abstract We thank the reviewer for the constructive comments. In response, randomization has been explicitly stated in the Methods section of the abstract. In addition, the primary ... Continue reading 1.Title and Abstract We thank the reviewer for the constructive comments. In response, randomization has been explicitly stated in the Methods section of the abstract. In addition, the primary (cataract severity) and secondary (oxidative stress markers and antioxidant enzyme activities) outcomes have been clearly defined. To further strengthen the abstract, a brief sentence highlighting the potential clinical and translational relevance of oxidative stress modulation in cataract has been added to the Introduction, while preserving the original structure and wording of the abstract. 2.Introduction We thank the reviewer for the constructive comments. To address the first concern, we have explicitly stated the study hypothesis at the end of the Introduction, while preserving the original structure of the section. Regarding the epidemiological claim on the global burden of cataract, the reference has been updated to authoritative population-based and global burden sources to ensure that prevalence-related statements are supported by appropriate epidemiological evidence. 3. Materials and Methods We thank the reviewer for the detailed and constructive comments regarding the Materials and Methods section. In response to these suggestions, several clarifications and additions have been made while preserving the original structure of the manuscript. First, we have clarified the rationale for each experimental group by explicitly describing the purpose of the control, selenite-only, DMSO, and apocynin treatment arms, including the assessment of dose-dependent effects. Second, the randomization procedure has been specified in greater detail by stating that group allocation was performed using a computer-generated random number sequence. Third, justification for the selected sample size (n = 7 per group) has been added based on previous experimental studies using the selenite-induced cataract model and ethical considerations aimed at minimizing animal use. Fourth, the rationale for the selected apocynin doses has been clarified with reference to prior in vivo studies demonstrating antioxidant and cytoprotective effects without overt toxicity. These doses were chosen to allow assessment of potential dose-dependent responses rather than pharmacokinetic characterization. Fifth, to address concerns regarding potential observer-related bias in cataract grading, we have expanded the description of bias-minimizing measures, including standardized illumination and magnification, predefined grading criteria, repeated assessments, and masking of the examiner to group allocation. Finally, the experimental timeline has been clarified within the text by explicitly stating the timing of selenite administration, treatment duration, and the points at which cataract assessment and tissue collection were performed. We believe that these revisions address the reviewer’s concerns and improve the methodological transparency and clarity of the study. 4. Results We thank the reviewer for the positive assessment of the Results section and for the constructive statistical and presentation-related comments. In response, several clarifications have been incorporated to improve transparency and interpretation while preserving the original results. Regarding Table 2, we acknowledge that the presentation of individual lens-level cataract grades may appear confusing without clarification. The table was intentionally designed to display individual lens-level data to ensure transparency of morphological findings. To address concerns about duplication and pseudo-replication, we have clarified in both the Results section and the table footnote that all statistical analyses were performed at the animal level, with bilateral lens findings summarized per rat. We also acknowledge that cataract grading represents ordinal data. Accordingly, we have clarified that mean values are presented for descriptive comparison across groups, while non-parametric statistical tests were applied for group comparisons, as specified in the Methods section. To address concerns regarding pseudo-replication and potential inflation of sample size, we have explicitly stated that cataract grading analyses were conducted at the animal level rather than treating bilateral lenses as independent observations. In response to the comment regarding the boxplots, we have clarified that these figures were included to visually illustrate the distribution and variability of biochemical parameters across groups and to complement the tabulated summary statistics. Finally, to improve clarity regarding statistical reporting, we have specified that statistically significant overall group differences were followed by predefined post-hoc pairwise comparisons, with corresponding p-values reported for the relevant group contrasts. We believe that these clarifications adequately address the reviewer’s concerns and further enhance the clarity and robustness of the Results section. 5.Discussion We thank the reviewer for the thoughtful and insightful comments regarding the mechanistic interpretation in the Discussion section. We agree that direct validation of NADPH oxidase activity or downstream redox signaling pathways (such as Nrf2 signaling) was beyond the scope of the present study. In response, we have revised the Discussion to moderate the mechanistic claims and to clarify that the proposed involvement of NADPH oxidase inhibition represents a plausible and mechanistically distinct explanation rather than a directly validated pathway. Comparative language implying superiority over other antioxidant agents has been softened, and apocynin is now discussed as a compound that may act through a different level of redox modulation rather than as a more effective or upstream intervention. In addition, we have explicitly acknowledged this limitation in the limitations subsection to ensure transparent interpretation of the findings. We believe these revisions appropriately align the Discussion with the experimental evidence while preserving the scientific rationale and relevance of the study. 1.Title and Abstract We thank the reviewer for the constructive comments. In response, randomization has been explicitly stated in the Methods section of the abstract. In addition, the primary (cataract severity) and secondary (oxidative stress markers and antioxidant enzyme activities) outcomes have been clearly defined. To further strengthen the abstract, a brief sentence highlighting the potential clinical and translational relevance of oxidative stress modulation in cataract has been added to the Introduction, while preserving the original structure and wording of the abstract. 2.Introduction We thank the reviewer for the constructive comments. To address the first concern, we have explicitly stated the study hypothesis at the end of the Introduction, while preserving the original structure of the section. Regarding the epidemiological claim on the global burden of cataract, the reference has been updated to authoritative population-based and global burden sources to ensure that prevalence-related statements are supported by appropriate epidemiological evidence. 3. Materials and Methods We thank the reviewer for the detailed and constructive comments regarding the Materials and Methods section. In response to these suggestions, several clarifications and additions have been made while preserving the original structure of the manuscript. First, we have clarified the rationale for each experimental group by explicitly describing the purpose of the control, selenite-only, DMSO, and apocynin treatment arms, including the assessment of dose-dependent effects. Second, the randomization procedure has been specified in greater detail by stating that group allocation was performed using a computer-generated random number sequence. Third, justification for the selected sample size (n = 7 per group) has been added based on previous experimental studies using the selenite-induced cataract model and ethical considerations aimed at minimizing animal use. Fourth, the rationale for the selected apocynin doses has been clarified with reference to prior in vivo studies demonstrating antioxidant and cytoprotective effects without overt toxicity. These doses were chosen to allow assessment of potential dose-dependent responses rather than pharmacokinetic characterization. Fifth, to address concerns regarding potential observer-related bias in cataract grading, we have expanded the description of bias-minimizing measures, including standardized illumination and magnification, predefined grading criteria, repeated assessments, and masking of the examiner to group allocation. Finally, the experimental timeline has been clarified within the text by explicitly stating the timing of selenite administration, treatment duration, and the points at which cataract assessment and tissue collection were performed. We believe that these revisions address the reviewer’s concerns and improve the methodological transparency and clarity of the study. 4. Results We thank the reviewer for the positive assessment of the Results section and for the constructive statistical and presentation-related comments. In response, several clarifications have been incorporated to improve transparency and interpretation while preserving the original results. Regarding Table 2, we acknowledge that the presentation of individual lens-level cataract grades may appear confusing without clarification. The table was intentionally designed to display individual lens-level data to ensure transparency of morphological findings. To address concerns about duplication and pseudo-replication, we have clarified in both the Results section and the table footnote that all statistical analyses were performed at the animal level, with bilateral lens findings summarized per rat. We also acknowledge that cataract grading represents ordinal data. Accordingly, we have clarified that mean values are presented for descriptive comparison across groups, while non-parametric statistical tests were applied for group comparisons, as specified in the Methods section. To address concerns regarding pseudo-replication and potential inflation of sample size, we have explicitly stated that cataract grading analyses were conducted at the animal level rather than treating bilateral lenses as independent observations. In response to the comment regarding the boxplots, we have clarified that these figures were included to visually illustrate the distribution and variability of biochemical parameters across groups and to complement the tabulated summary statistics. Finally, to improve clarity regarding statistical reporting, we have specified that statistically significant overall group differences were followed by predefined post-hoc pairwise comparisons, with corresponding p-values reported for the relevant group contrasts. We believe that these clarifications adequately address the reviewer’s concerns and further enhance the clarity and robustness of the Results section. 5.Discussion We thank the reviewer for the thoughtful and insightful comments regarding the mechanistic interpretation in the Discussion section. We agree that direct validation of NADPH oxidase activity or downstream redox signaling pathways (such as Nrf2 signaling) was beyond the scope of the present study. In response, we have revised the Discussion to moderate the mechanistic claims and to clarify that the proposed involvement of NADPH oxidase inhibition represents a plausible and mechanistically distinct explanation rather than a directly validated pathway. Comparative language implying superiority over other antioxidant agents has been softened, and apocynin is now discussed as a compound that may act through a different level of redox modulation rather than as a more effective or upstream intervention. In addition, we have explicitly acknowledged this limitation in the limitations subsection to ensure transparent interpretation of the findings. We believe these revisions appropriately align the Discussion with the experimental evidence while preserving the scientific rationale and relevance of the study. Competing Interests: The authors declare that they have no competing interests. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 14 Feb 2026 Hülya adıgüzel okşar , Department of Ophtalmology, Bolu Abant Izzet Baysal University, Training and Research Hospital, Bolu, Turkey 14 Feb 2026 Author Response 1.Title and Abstract We thank the reviewer for the constructive comments. In response, randomization has been explicitly stated in the Methods section of the abstract. In addition, the primary ... Continue reading 1.Title and Abstract We thank the reviewer for the constructive comments. In response, randomization has been explicitly stated in the Methods section of the abstract. In addition, the primary (cataract severity) and secondary (oxidative stress markers and antioxidant enzyme activities) outcomes have been clearly defined. To further strengthen the abstract, a brief sentence highlighting the potential clinical and translational relevance of oxidative stress modulation in cataract has been added to the Introduction, while preserving the original structure and wording of the abstract. 2.Introduction We thank the reviewer for the constructive comments. To address the first concern, we have explicitly stated the study hypothesis at the end of the Introduction, while preserving the original structure of the section. Regarding the epidemiological claim on the global burden of cataract, the reference has been updated to authoritative population-based and global burden sources to ensure that prevalence-related statements are supported by appropriate epidemiological evidence. 3. Materials and Methods We thank the reviewer for the detailed and constructive comments regarding the Materials and Methods section. In response to these suggestions, several clarifications and additions have been made while preserving the original structure of the manuscript. First, we have clarified the rationale for each experimental group by explicitly describing the purpose of the control, selenite-only, DMSO, and apocynin treatment arms, including the assessment of dose-dependent effects. Second, the randomization procedure has been specified in greater detail by stating that group allocation was performed using a computer-generated random number sequence. Third, justification for the selected sample size (n = 7 per group) has been added based on previous experimental studies using the selenite-induced cataract model and ethical considerations aimed at minimizing animal use. Fourth, the rationale for the selected apocynin doses has been clarified with reference to prior in vivo studies demonstrating antioxidant and cytoprotective effects without overt toxicity. These doses were chosen to allow assessment of potential dose-dependent responses rather than pharmacokinetic characterization. Fifth, to address concerns regarding potential observer-related bias in cataract grading, we have expanded the description of bias-minimizing measures, including standardized illumination and magnification, predefined grading criteria, repeated assessments, and masking of the examiner to group allocation. Finally, the experimental timeline has been clarified within the text by explicitly stating the timing of selenite administration, treatment duration, and the points at which cataract assessment and tissue collection were performed. We believe that these revisions address the reviewer’s concerns and improve the methodological transparency and clarity of the study. 4. Results We thank the reviewer for the positive assessment of the Results section and for the constructive statistical and presentation-related comments. In response, several clarifications have been incorporated to improve transparency and interpretation while preserving the original results. Regarding Table 2, we acknowledge that the presentation of individual lens-level cataract grades may appear confusing without clarification. The table was intentionally designed to display individual lens-level data to ensure transparency of morphological findings. To address concerns about duplication and pseudo-replication, we have clarified in both the Results section and the table footnote that all statistical analyses were performed at the animal level, with bilateral lens findings summarized per rat. We also acknowledge that cataract grading represents ordinal data. Accordingly, we have clarified that mean values are presented for descriptive comparison across groups, while non-parametric statistical tests were applied for group comparisons, as specified in the Methods section. To address concerns regarding pseudo-replication and potential inflation of sample size, we have explicitly stated that cataract grading analyses were conducted at the animal level rather than treating bilateral lenses as independent observations. In response to the comment regarding the boxplots, we have clarified that these figures were included to visually illustrate the distribution and variability of biochemical parameters across groups and to complement the tabulated summary statistics. Finally, to improve clarity regarding statistical reporting, we have specified that statistically significant overall group differences were followed by predefined post-hoc pairwise comparisons, with corresponding p-values reported for the relevant group contrasts. We believe that these clarifications adequately address the reviewer’s concerns and further enhance the clarity and robustness of the Results section. 5.Discussion We thank the reviewer for the thoughtful and insightful comments regarding the mechanistic interpretation in the Discussion section. We agree that direct validation of NADPH oxidase activity or downstream redox signaling pathways (such as Nrf2 signaling) was beyond the scope of the present study. In response, we have revised the Discussion to moderate the mechanistic claims and to clarify that the proposed involvement of NADPH oxidase inhibition represents a plausible and mechanistically distinct explanation rather than a directly validated pathway. Comparative language implying superiority over other antioxidant agents has been softened, and apocynin is now discussed as a compound that may act through a different level of redox modulation rather than as a more effective or upstream intervention. In addition, we have explicitly acknowledged this limitation in the limitations subsection to ensure transparent interpretation of the findings. We believe these revisions appropriately align the Discussion with the experimental evidence while preserving the scientific rationale and relevance of the study. 1.Title and Abstract We thank the reviewer for the constructive comments. In response, randomization has been explicitly stated in the Methods section of the abstract. In addition, the primary (cataract severity) and secondary (oxidative stress markers and antioxidant enzyme activities) outcomes have been clearly defined. To further strengthen the abstract, a brief sentence highlighting the potential clinical and translational relevance of oxidative stress modulation in cataract has been added to the Introduction, while preserving the original structure and wording of the abstract. 2.Introduction We thank the reviewer for the constructive comments. To address the first concern, we have explicitly stated the study hypothesis at the end of the Introduction, while preserving the original structure of the section. Regarding the epidemiological claim on the global burden of cataract, the reference has been updated to authoritative population-based and global burden sources to ensure that prevalence-related statements are supported by appropriate epidemiological evidence. 3. Materials and Methods We thank the reviewer for the detailed and constructive comments regarding the Materials and Methods section. In response to these suggestions, several clarifications and additions have been made while preserving the original structure of the manuscript. First, we have clarified the rationale for each experimental group by explicitly describing the purpose of the control, selenite-only, DMSO, and apocynin treatment arms, including the assessment of dose-dependent effects. Second, the randomization procedure has been specified in greater detail by stating that group allocation was performed using a computer-generated random number sequence. Third, justification for the selected sample size (n = 7 per group) has been added based on previous experimental studies using the selenite-induced cataract model and ethical considerations aimed at minimizing animal use. Fourth, the rationale for the selected apocynin doses has been clarified with reference to prior in vivo studies demonstrating antioxidant and cytoprotective effects without overt toxicity. These doses were chosen to allow assessment of potential dose-dependent responses rather than pharmacokinetic characterization. Fifth, to address concerns regarding potential observer-related bias in cataract grading, we have expanded the description of bias-minimizing measures, including standardized illumination and magnification, predefined grading criteria, repeated assessments, and masking of the examiner to group allocation. Finally, the experimental timeline has been clarified within the text by explicitly stating the timing of selenite administration, treatment duration, and the points at which cataract assessment and tissue collection were performed. We believe that these revisions address the reviewer’s concerns and improve the methodological transparency and clarity of the study. 4. Results We thank the reviewer for the positive assessment of the Results section and for the constructive statistical and presentation-related comments. In response, several clarifications have been incorporated to improve transparency and interpretation while preserving the original results. Regarding Table 2, we acknowledge that the presentation of individual lens-level cataract grades may appear confusing without clarification. The table was intentionally designed to display individual lens-level data to ensure transparency of morphological findings. To address concerns about duplication and pseudo-replication, we have clarified in both the Results section and the table footnote that all statistical analyses were performed at the animal level, with bilateral lens findings summarized per rat. We also acknowledge that cataract grading represents ordinal data. Accordingly, we have clarified that mean values are presented for descriptive comparison across groups, while non-parametric statistical tests were applied for group comparisons, as specified in the Methods section. To address concerns regarding pseudo-replication and potential inflation of sample size, we have explicitly stated that cataract grading analyses were conducted at the animal level rather than treating bilateral lenses as independent observations. In response to the comment regarding the boxplots, we have clarified that these figures were included to visually illustrate the distribution and variability of biochemical parameters across groups and to complement the tabulated summary statistics. Finally, to improve clarity regarding statistical reporting, we have specified that statistically significant overall group differences were followed by predefined post-hoc pairwise comparisons, with corresponding p-values reported for the relevant group contrasts. We believe that these clarifications adequately address the reviewer’s concerns and further enhance the clarity and robustness of the Results section. 5.Discussion We thank the reviewer for the thoughtful and insightful comments regarding the mechanistic interpretation in the Discussion section. We agree that direct validation of NADPH oxidase activity or downstream redox signaling pathways (such as Nrf2 signaling) was beyond the scope of the present study. In response, we have revised the Discussion to moderate the mechanistic claims and to clarify that the proposed involvement of NADPH oxidase inhibition represents a plausible and mechanistically distinct explanation rather than a directly validated pathway. Comparative language implying superiority over other antioxidant agents has been softened, and apocynin is now discussed as a compound that may act through a different level of redox modulation rather than as a more effective or upstream intervention. In addition, we have explicitly acknowledged this limitation in the limitations subsection to ensure transparent interpretation of the findings. We believe these revisions appropriately align the Discussion with the experimental evidence while preserving the scientific rationale and relevance of the study. Competing Interests: The authors declare that they have no competing interests. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 13 Jan 2026 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 3 (revision) 15 Apr 26 read read Version 2 (revision) 14 Feb 26 read read Version 1 13 Jan 26 read read Syska Widyawati , University of Indonesia, Jakarta, Indonesia Rajesh Choudhary , Shri Shankaracharya Professional University, Chhattisgarh, India Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Widyawati S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 30 Apr 2026 | for Version 3 Syska Widyawati , University of Indonesia, Jakarta, Indonesia 0 Views copyright © 2026 Widyawati S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The introduction has improved significantly compared with the previous version, and the overall rationale is now clearer and more structured. However, modern cataract surgery safety and efficacy and the alternative suggestions should not be taken from reference no. 2. The flow from oxidative stress, antioxidant therapy, the use of the selenite model, and finally the rationale for apocynin is already well presented. Since apocynin is the main subject of the study, the introduction should more clearly explain from the beginning what is already known about apocynin, what has been studied in previous experimental models, and why a gap still exists in cataract research. For example, if apocynin has shown protective effects in other oxidative stress-related tissues through NADPH oxidase inhibition, this should be linked more directly to lens biology and cataractogenesis. The selection of oxidative stress biomarkers, especially glutathione reductase (GR), may also need a stronger justification. Since many cataract studies focus more on GSH or GPx, explaining why GR was chosen in this study MATERIAL AND METHODS: the timeline needs better consistency. The manuscript states that sodium selenite was administered on postnatal day 10, followed by treatment for 7 consecutive days, but cataract assessment and tissue collection were performed on day 14. This creates confusion because seven days of treatment from day 10 would normally extend to day 17.The exact sequence of induction, treatment initiation, and sacrifice should be stated more clearly to avoid ambiguity. The sample size of seven animals per group should be justified. There is no explanation of whether this number was based on a formal power calculation, previous literature, or ethical reduction principles The concentration and final injection volume of DMSO as a vehicle control should be reported, since DMSO may have biological effects depending on dose may influence oxidative stress biomarkers The description of the laboratory location is inconsistent. Earlier, biochemical analyses were stated to be performed in the Biochemistry Laboratory, while here it is described as the Department of Medical Microbiology. This should be corrected for consistency. RESULT The biological difference between grade 1 and grade 2 may not be equivalent to that between grade 4 and grade 5. This may create overinterpretation of precision and may not accurately reflect the true distribution of lens opacity severity. Therefore, reporting it primarily as mean ± SD may still be methodologically questionable. Reporting median (IQR) or frequency distribution across grades would be statistically more appropriate and more consistent with the use of non-parametric analysis. DISCUSSION AND CONCLUSSION The Discussion section is well structured and the dose-dependent effects of apocynin are interpreted in a logical and clinically relevant way However, since NADPH oxidase activity, NOX expression, Nrf2 signaling, and apoptotic markers were not evaluated, the proposed mechanism of action should be presented more clearly as a plausible hypothesis rather than a confirmed pathway Discussion of DMSO as a biologically active vehicle should be also included Translational claims regarding human cataract prevention should be more moderate Competing Interests No competing interests were disclosed. Reviewer Expertise cornea cataract and refractive surgery I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Widyawati S. Peer Review Report For: THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.5256/f1000research.198022.r475290) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/15-50/v3#referee-response-475290 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Choudhary R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 24 Apr 2026 | for Version 3 Rajesh Choudhary , Shri Shankaracharya Professional University, Chhattisgarh, Chhattisgarh, India 0 Views copyright © 2026 Choudhary R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions still needs to clarify on statistical indicator used in Table 3, a-h, define the each like aP<0.05 vs Group 1 or ? to clarity of comparison group. Competing Interests No competing interests were disclosed. Reviewer Expertise Diabetes, Cataract I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Choudhary R. Peer Review Report For: THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.5256/f1000research.198022.r475289) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/15-50/v3#referee-response-475289 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Widyawati S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 13 Mar 2026 | for Version 2 Syska Widyawati , University of Indonesia, Jakarta, Indonesia 0 Views copyright © 2026 Widyawati S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions introduction: The authors have made substantial improvements to the manuscript. The hypothesis is now clearly stated, and the inclusion of additional epidemiological references strengthens the background section. However, several sentences would benefit from further language editing. For example, the introductory statement describing apocynin should be revised for grammatical accuracy and clarity methods: The experimental design includes a Na₂SeO₃-only group and a Na₂SeO₃ + DMSO group. While this likely serves to distinguish disease induction from potential solvent effects, the rationale for including the DMSO vehicle control is not clearly explained in the Methods section. I recommend that the authors explicitly clarify the purpose of each experimental group to improve methodological transparency. The methodology for cataract grading and biochemical analysis is already well described, and the authors implemented several measures to reduce observational bias, this would be better if the method already previously validated. The description of the euthanasia procedure should be describe clearer to ensure compliance with animal welfare standards. Result: Despite the revisions, Table 2 still summarizes the cataract grading data using mean and min–max values, which implies treatment of the variable as continuous. However, the cataract grading system is an ordinal categorical scale, and therefore this type of statistical summary is not appropriate. The authors should revise the presentation and statistical reporting to align with the ordinal nature of the data. Competing Interests No competing interests were disclosed. Reviewer Expertise cornea cataract and refractive surgery I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 24 Mar 2026 Hülya adıgüzel okşar, Department of Ophtalmology, Bolu Abant Izzet Baysal University, Training and Research Hospital, Bolu, Turkey We sincerely thank the reviewer for the careful evaluation of our manuscript and for the constructive and valuable suggestions. We have revised the manuscript accordingly, and our point-by-point responses are provided below. Introduction: We appreciate the reviewer’s positive comments regarding the clarity of the hypothesis and the strengthened background. In line with the suggestion, the sentence describing apocynin has been revised to improve grammatical accuracy, clarity, and overall readability. Methods: Thank you for highlighting the need for clearer methodological transparency. We have revised the Methods section to explicitly clarify the rationale for each experimental group. In particular, the purpose of the DMSO-treated group has now been clearly stated as a vehicle control to distinguish potential solvent effects from those of apocynin treatment. In addition, the description of the euthanasia procedure has been improved to ensure clarity and compliance with animal welfare standards. The revised text now explicitly states that euthanasia was performed under deep anesthesia and in accordance with institutional and international guidelines.We also appreciate the suggestion regarding methodological validation. The cataract grading and biochemical analysis methods used in this study are well-established in the literature, and we have clarified this point in the revised manuscript to further support methodological reliability and reduce potential observational bias. Results (Table 2 – Ordinal Data): We thank the reviewer for this important observation. We agree that cataract grading represents an ordinal categorical scale and should be interpreted accordingly. In the revised manuscript, we have clarified that mean values presented in Table 2 are provided for descriptive purposes only, while all statistical analyses were conducted using appropriate non-parametric methods.Furthermore, we have emphasized that individual lens-level cataract grading data are presented in Table 2 to ensure full transparency and to allow direct interpretation of the ordinal data distribution. These revisions improve the clarity, methodological accuracy, and interpretability of the data presentation. We believe that the manuscript has been substantially improved in response to the reviewer’s comments and that all concerns have been adequately addressed. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Widyawati S. Peer Review Report For: THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.5256/f1000research.196401.r458568) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/15-50/v2#referee-response-458568 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Choudhary R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 20 Feb 2026 | for Version 2 Rajesh Choudhary , Shri Shankaracharya Professional University, Chhattisgarh, Chhattisgarh, India 0 Views copyright © 2026 Choudhary R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors addressed my concern, but it is not reflected in the tables and/or figures' footnotes or captions like #P < 0.05 vs. Group I or Group II like that. Because without comparing the disease control group vs. the treatment group, we can't understand the effects of treatments. All tables and figures must be self-explanatory. mentions all statistical indicators or parameters in the footnote also for better transparency. Changes should also be made in respective figures. Competing Interests No competing interests were disclosed. Reviewer Expertise Diabetes, Cataract I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 24 Mar 2026 Hülya adıgüzel okşar, Department of Ophtalmology, Bolu Abant Izzet Baysal University, Training and Research Hospital, Bolu, Turkey Thank you for this important and constructive comment. In response, we have revised both the tables and figures to ensure that all results are fully self-explanatory and that all statistical comparisons are clearly and transparently presented. First, Table 3 has been updated to incorporate post hoc multiple comparison results. Statistically significant differences between groups are now indicated using superscript letters (a–h), where groups sharing the same letter are not significantly different, and different letters indicate statistically significant differences (p < 0.05, one-way ANOVA followed by Tukey post hoc test). In addition, the table footnote has been expanded to explicitly clarify that comparisons relative to both the control group and the selenite-induced cataract group (Group 1) were evaluated, thereby improving interpretability of treatment effects. Second, all figures (Figures 2–4) have been revised accordingly. In addition to comparisons versus the control group (*, **, ***), statistically significant differences between experimental groups, particularly between the treatment groups and the selenite-induced cataract group, are now explicitly indicated using additional symbols (#, †, ‡), each clearly defined in the corresponding figure legends. Furthermore, all figure legends have been updated to explicitly define each group and all statistical annotations, ensuring that the figures are fully interpretable as standalone elements. We believe that these revisions substantially improve the clarity, transparency, and interpretability of the data presentation and fully address the reviewer’s concern. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Choudhary R. Peer Review Report For: THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.5256/f1000research.196401.r458569) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/15-50/v2#referee-response-458569 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Choudhary R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 06 Feb 2026 | for Version 1 Rajesh Choudhary , Shri Shankaracharya Professional University, Chhattisgarh, Chhattisgarh, India 0 Views copyright © 2026 Choudhary R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Authors explore the protective effects of apocynin on cataract formation. The authors well explained the research background and concluded the research with their results. During the statistical analysis, why was the data of the apocynin-treated group (Group III and IV) were not compared with Group I or II in results table or figure. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Diabetes, Cataract I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 14 Feb 2026 Hülya adıgüzel okşar, Department of Ophtalmology, Bolu Abant Izzet Baysal University, Training and Research Hospital, Bolu, Turkey We thank the reviewer for the positive and constructive evaluation of our manuscript. Regarding the statistical analysis, we would like to clarify that following statistically significant overall group differences, post-hoc pairwise comparisons were performed as specified in the Methods section. In these analyses, apocynin-treated groups (Groups III and IV) were compared with both the selenite-only group (Group I) and the DMSO group (Group II). These comparisons demonstrated that apocynin-treated groups exhibited significantly more favorable oxidative stress profiles and reduced cataract severity. To improve clarity and transparency, we have now explicitly stated this in the Results section. We appreciate the reviewer’s careful assessment of the statistical interpretation and thank them for their overall positive evaluation of the study. View more View less Competing Interests The authors declare that they have no competing interests. reply Respond Report a concern Choudhary R. Peer Review Report For: THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.5256/f1000research.192115.r450308) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/15-50/v1#referee-response-450308 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Widyawati S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 06 Feb 2026 | for Version 1 Syska Widyawati , University of Indonesia, Jakarta, Indonesia 0 Views copyright © 2026 Widyawati S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions 1. Title and Abstract Strengths The title accurately reflects the topic and research model The abstract summarizes objectives, interventions, and principal outcomes. Concerns Randomization is stated but not explicitly highlighted in the abstract and the title The introduction of the abstract currently states only the aim of the study without providing sufficient context regarding the scientific or clinical importance of the research Primary versus secondary outcomes are not clearly distinguished in the abstract 2. Introduction Strengths Well-structured background with appropriate citation of oxidative stress in cataractogenesis, with a clear identification of a knowledge gap regarding apocynin in lens tissue. Concerns The hypothesis is implied rather than explicitly stated. The citation about the magnitude of cataract problems cited from other study that were not epidemiology of cataract. For claims related to the prevalence of cataract, its contribution to global blindness, or its public health burden, the authors should cite authoritative epidemiological sources, such as population-based studies, systematic reviews, or global burden analyses (e.g., WHO or Global Burden of Disease reports). 3. Methods 3.1 Trial Design Strengths Ethical clearance mentioned clear description and uniformity of the experimental animals. The use of age-matched, sex-matched Sprague–Dawley rats with a clearly defined postnatal age and body weight enhances internal validity and reduces biological variability that could confound oxidative stress–related outcomes Doses, routes, duration, and vehicles are clearly specified. The biochemical analyses are clearly described and based on well-established, standardized methods. Concerns While the study includes multiple experimental groups, the manuscript does not sufficiently justify the rationale for including each group or clearly explain the specific purpose of each treatment arm within the study design No schematic timeline of interventions and assessments. The study is randomized but the method is insufficiently detailed. Justification for sample size (n=7 per group) is absent or sample size calculation preferred No pharmacokinetic rationale for selected apocynin doses The morphological evaluation of lens opacity relies on a grading system developed by the authors and assessed by a single examiner. Although the examiner was reported to be blinded to group allocation, this approach remains inherently subjective and may introduce observer-related bias, particularly because cataract grade is a key comparative outcome between experimental groups Results Strengths Clear presentation of cataract grades and biochemical data. Figures are generally interpretable and consistent with tables. Dose-dependent divergence between antioxidant and pro-oxidant effects is convincingly shown. The table already provides mean ± SD and min–max values, which sufficiently describe central tendency and dispersion for the reported comparisons. Concerns Table 2 formatting is confusing and appears duplicated. Cataract grading scales are inherently ordinal, reflecting increasing severity categories rather than equal-interval continuous measurements. As such, the use of means assumes equal distance between grades, which may not accurately reflect the biological or optical progression of lens opacity. This approach may therefore introduce bias and potentially overstate precision when comparing groups Two lenses from one rat are not independent (shared genetics, environment, exposure). Treating them as independent inflates sample size and can make p-values artificially small (pseudo-replication) Without additional emphasis on distributional features (e.g., skewness or outliers), the boxplots appear largely redundant rather than complementary. A statistically significant omnibus (multivariate or overall) test should be followed by clearly defined and consistently reported post-hoc pairwise comparisons to determine where the differences lie Discussion Strengths Thoughtful interpretation of dose-dependent redox effects. Integration with broader antioxidant literature is appropriate. Limitations are openly acknowledged. Key Scientific Limitation Lack of mechanistic validation (e.g., NADPH oxidase activity, Nrf2 signaling). Stating that apocynin inhibits NADPH oxidase does not fully explain how this mechanism translates into superior or more upstream protection compared with conventional antioxidants that primarily act as reactive oxygen species scavengers. If the authors wish to argue that apocynin is more effective than other antioxidant agents previously tested in cataract models, a clearer mechanistic framework is required Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise cornea cataract and refractive surgery I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 14 Feb 2026 Hülya adıgüzel okşar, Department of Ophtalmology, Bolu Abant Izzet Baysal University, Training and Research Hospital, Bolu, Turkey 1.Title and Abstract We thank the reviewer for the constructive comments. In response, randomization has been explicitly stated in the Methods section of the abstract. In addition, the primary (cataract severity) and secondary (oxidative stress markers and antioxidant enzyme activities) outcomes have been clearly defined. To further strengthen the abstract, a brief sentence highlighting the potential clinical and translational relevance of oxidative stress modulation in cataract has been added to the Introduction, while preserving the original structure and wording of the abstract. 2.Introduction We thank the reviewer for the constructive comments. To address the first concern, we have explicitly stated the study hypothesis at the end of the Introduction, while preserving the original structure of the section. Regarding the epidemiological claim on the global burden of cataract, the reference has been updated to authoritative population-based and global burden sources to ensure that prevalence-related statements are supported by appropriate epidemiological evidence. 3. Materials and Methods We thank the reviewer for the detailed and constructive comments regarding the Materials and Methods section. In response to these suggestions, several clarifications and additions have been made while preserving the original structure of the manuscript. First, we have clarified the rationale for each experimental group by explicitly describing the purpose of the control, selenite-only, DMSO, and apocynin treatment arms, including the assessment of dose-dependent effects. Second, the randomization procedure has been specified in greater detail by stating that group allocation was performed using a computer-generated random number sequence. Third, justification for the selected sample size (n = 7 per group) has been added based on previous experimental studies using the selenite-induced cataract model and ethical considerations aimed at minimizing animal use. Fourth, the rationale for the selected apocynin doses has been clarified with reference to prior in vivo studies demonstrating antioxidant and cytoprotective effects without overt toxicity. These doses were chosen to allow assessment of potential dose-dependent responses rather than pharmacokinetic characterization. Fifth, to address concerns regarding potential observer-related bias in cataract grading, we have expanded the description of bias-minimizing measures, including standardized illumination and magnification, predefined grading criteria, repeated assessments, and masking of the examiner to group allocation. Finally, the experimental timeline has been clarified within the text by explicitly stating the timing of selenite administration, treatment duration, and the points at which cataract assessment and tissue collection were performed. We believe that these revisions address the reviewer’s concerns and improve the methodological transparency and clarity of the study. 4. Results We thank the reviewer for the positive assessment of the Results section and for the constructive statistical and presentation-related comments. In response, several clarifications have been incorporated to improve transparency and interpretation while preserving the original results. Regarding Table 2, we acknowledge that the presentation of individual lens-level cataract grades may appear confusing without clarification. The table was intentionally designed to display individual lens-level data to ensure transparency of morphological findings. To address concerns about duplication and pseudo-replication, we have clarified in both the Results section and the table footnote that all statistical analyses were performed at the animal level, with bilateral lens findings summarized per rat. We also acknowledge that cataract grading represents ordinal data. Accordingly, we have clarified that mean values are presented for descriptive comparison across groups, while non-parametric statistical tests were applied for group comparisons, as specified in the Methods section. To address concerns regarding pseudo-replication and potential inflation of sample size, we have explicitly stated that cataract grading analyses were conducted at the animal level rather than treating bilateral lenses as independent observations. In response to the comment regarding the boxplots, we have clarified that these figures were included to visually illustrate the distribution and variability of biochemical parameters across groups and to complement the tabulated summary statistics. Finally, to improve clarity regarding statistical reporting, we have specified that statistically significant overall group differences were followed by predefined post-hoc pairwise comparisons, with corresponding p-values reported for the relevant group contrasts. We believe that these clarifications adequately address the reviewer’s concerns and further enhance the clarity and robustness of the Results section. 5.Discussion We thank the reviewer for the thoughtful and insightful comments regarding the mechanistic interpretation in the Discussion section. We agree that direct validation of NADPH oxidase activity or downstream redox signaling pathways (such as Nrf2 signaling) was beyond the scope of the present study. In response, we have revised the Discussion to moderate the mechanistic claims and to clarify that the proposed involvement of NADPH oxidase inhibition represents a plausible and mechanistically distinct explanation rather than a directly validated pathway. Comparative language implying superiority over other antioxidant agents has been softened, and apocynin is now discussed as a compound that may act through a different level of redox modulation rather than as a more effective or upstream intervention. In addition, we have explicitly acknowledged this limitation in the limitations subsection to ensure transparent interpretation of the findings. We believe these revisions appropriately align the Discussion with the experimental evidence while preserving the scientific rationale and relevance of the study. View more View less Competing Interests The authors declare that they have no competing interests. reply Respond Report a concern Widyawati S. Peer Review Report For: THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT MODEL [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :50 ( https://doi.org/10.5256/f1000research.192115.r451976) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/15-50/v1#referee-response-451976 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Stay Updated Sign up for content alerts and receive a weekly or monthly email with all newly published articles Register with F1000Research Already registered? Sign in Not now, thanks close PLEASE NOTE If you are an AUTHOR of this article, please check that you signed in with the account associated with this article otherwise we cannot automatically identify your role as an author and your comment will be labelled as a “User Comment”. If you are a REVIEWER of this article, please check that you have signed in with the account associated with this article and then go to your account to submit your report, please do not post your review here. If you do not have access to your original account, please contact us . All commenters must hold a formal affiliation as per our Policies . The information that you give us will be displayed next to your comment. User comments must be in English, comprehensible and relevant to the article under discussion. We reserve the right to remove any comments that we consider to be inappropriate, offensive or otherwise in breach of the User Comment Terms and Conditions . Commenters must not use a comment for personal attacks. When criticisms of the article are based on unpublished data, the data should be made available. I accept the User Comment Terms and Conditions Please confirm that you accept the User Comment Terms and Conditions. Affiliation ✕ refresh Please enter your institution. Note: To add your institution or organisation, start typing the name and then select the correct name from the list. Where applicable, the name will appear in both the original language and in English. Do not paste in the name. If the name does not appear in the drop-down list, we will display the information you have entered. ✕ refresh Country/Region * USA UK Canada China France Germany Afghanistan Aland Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory British Virgin Islands Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Cook Islands Costa Rica Cote d'Ivoire Croatia Cuba Cyprus Czech Republic Democratic Republic of the Congo Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Federated States of Micronesia Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and Mcdonald Islands Holy See (Vatican City State) Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Kosovo (Serbia and Montenegro) Kuwait Kyrgyzstan Lao People's Democratic Republic Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macao Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Minor Outlying Islands of the United States Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands Antilles New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island North Korea North Macedonia Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Reunion Romania Russian Federation Rwanda Saint Helena Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Is South Korea South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand The Gambia The Netherlands Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu UK USA Uganda Ukraine United Arab Emirates United States Virgin Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam Wallis and Futuna West Bank and Gaza Strip Western Sahara Yemen Zambia Zimbabwe Please select your country/region. You must enter a comment. Competing Interests Please disclose any competing interests that might be construed to influence your judgment of the article's or peer review report's validity or importance. Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Please state your competing interests The comment has been saved. An error has occurred. Please try again. Cancel Post var lTitle = "THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED...".replace("'", ''); var linkedInUrl = "http://www.linkedin.com/shareArticle?url=https://f1000research.com/articles/15-50/v1" + "&title=" + encodeURIComponent(lTitle) + "&summary=" + encodeURIComponent('Read the article by '); var deliciousUrl = "https://del.icio.us/post?url=https://f1000research.com/articles/15-50/v1&title=" + encodeURIComponent(lTitle); var redditUrl = "http://reddit.com/submit?url=https://f1000research.com/articles/15-50/v1" + "&title=" + encodeURIComponent(lTitle); linkedInUrl += encodeURIComponent('Adıgüzel Okşar H et al.'); var offsetTop = /chrome/i.test( navigator.userAgent ) ? 4 : -10; var addthis_config = { ui_offset_top: offsetTop, services_compact : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_expanded : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_custom : [ { name: "LinkedIn", url: linkedInUrl, icon:"/img/icon/at_linkedin.svg" }, { name: "Mendeley", url: "http://www.mendeley.com/import/?url=https://f1000research.com/articles/15-50/v1/mendeley", icon:"/img/icon/at_mendeley.svg" }, { name: "Reddit", url: redditUrl, icon:"/img/icon/at_reddit.svg" }, ] }; var addthis_share = { url: "https://f1000research.com/articles/15-50", templates : { twitter : "THE PROTECTIVE EFFECT OF APOCYNIN ON A SELENITE-INDUCED CATARACT.... Adıgüzel Okşar H et al., published by " + "@F1000Research" + ", https://f1000research.com/articles/15-50/v1" } }; if (typeof(addthis) != "undefined"){ addthis.addEventListener('addthis.ready', checkCount); addthis.addEventListener('addthis.menu.share', checkCount); } $(".f1r-shares-twitter").attr("href", "https://twitter.com/intent/tweet?text=" + addthis_share.templates.twitter); $(".f1r-shares-facebook").attr("href", "https://www.facebook.com/sharer/sharer.php?u=" + addthis_share.url); $(".f1r-shares-linkedin").attr("href", addthis_config.services_custom[0].url); $(".f1r-shares-reddit").attr("href", addthis_config.services_custom[2].url); $(".f1r-shares-mendelay").attr("href", addthis_config.services_custom[1].url); function checkCount(){ setTimeout(function(){ $(".addthis_button_expanded").each(function(){ var count = $(this).text(); if (count !== "" && count != "0") $(this).removeClass("is-hidden"); else $(this).addClass("is-hidden"); }); }, 1000); } close How to cite this report {{reportCitation}} Cancel Copy Citation Details $(function(){R.ui.buttonDropdowns('.dropdown-for-downloads');}); $(function(){R.ui.toolbarDropdowns('.toolbar-dropdown-for-downloads');}); $.get("/articles/acj/174231/192115") new F1000.Clipboard(); new F1000.ThesaurusTermsDisplay("articles", "article", "192115"); $(document).ready(function() { $( "#frame1" ).on('load', function() { var mydiv = $(this).contents().find("div"); var h = mydiv.height(); console.log(h) }); var tooltipLivingFigure = jQuery(".interactive-living-figure-label .icon-more-info"), titleLivingFigure = tooltipLivingFigure.attr("title"); tooltipLivingFigure.simpletip({ fixed: true, position: ["-115", "30"], baseClass: 'small-tooltip', content:titleLivingFigure + " " }); tooltipLivingFigure.removeAttr("title"); $("body").on("click", ".cite-living-figure", function(e) { e.preventDefault(); var ref = $(this).attr("data-ref"); $(this).closest(".living-figure-list-container").find("#" + ref).fadeIn(200); }); $("body").on("click", ".close-cite-living-figure", function(e) { e.preventDefault(); $(this).closest(".popup-window-wrapper").fadeOut(200); }); $(document).on("mouseup", function(e) { var metricsContainer = $(".article-metrics-popover-wrapper"); if (!metricsContainer.is(e.target) && metricsContainer.has(e.target).length === 0) { $(".article-metrics-close-button").click(); } }); var articleId = $('#articleId').val(); if($("#main-article-count-box").attachArticleMetrics) { $("#main-article-count-box").attachArticleMetrics(articleId, { articleMetricsView: true }); } }); var figshareWidget = $(".new_figshare_widget"); if (figshareWidget.length > 0) { window.figshare.load("f1000", function(Widget) { // Select a tag/tags defined in your page. In this tag we will place the widget. _.map(figshareWidget, function(el){ var widget = new Widget({ articleId: $(el).attr("figshare_articleId") //height:300 // this is the height of the viewer part. [Default: 550] }); widget.initialize(); // initialize the widget widget.mount(el); // mount it in a tag that's on your page // this will save the widget on the global scope for later use from // your JS scripts. This line is optional. //window.widget = widget; }); }); } close Error Close Add Reset F1000.MICROSERVICES.AFFILIATION = ''; $(document).ready(function () { $('.js-affiliations-form').each((index, form) => { new AffiliationForm({ formId: form.id, institutionErrorSelector: '.comment-enter-institution', departmentErrorSelector: '.comment-enter-department', placeSelector: '.js-add-comment-place', stateSelector: '.js-add-comment-state', zipCodeSelector: '.js-add-comment-zipcode', countrySelector: '.js-add-comment-country', countryErrorSelector: '.comment-enter-country', }); }); }); $(document).ready(function () { var reportIds = { "450310": 0, "450311": 0, "450308": 12, "450309": 0, "450306": 0, "450307": 0, "450304": 0, "450305": 0, "476175": 0, "465935": 0, "465934": 0, "465933": 0, "465932": 0, "465931": 0, "450312": 0, "450313": 0, "476183": 0, "476182": 0, "476181": 0, "476180": 0, "465940": 0, "476179": 0, "465939": 0, "476178": 0, "465938": 0, "476177": 0, "465937": 0, "476176": 0, "465936": 0, "463647": 0, "463646": 0, "463645": 0, "463644": 0, "463643": 0, "476184": 0, "463651": 0, "463650": 0, "463649": 0, "463648": 0, "482119": 0, "467527": 0, "482118": 0, "467526": 0, "482117": 0, "482116": 0, "482115": 0, "482114": 0, "482113": 0, "467535": 0, "467534": 0, "467533": 0, "467532": 0, "467531": 0, "482122": 0, "467530": 0, "482121": 0, "467529": 0, "458568": 6, "482120": 0, "458569": 10, "467528": 0, "451975": 0, "454030": 0, "451982": 0, "459151": 0, "454031": 0, "451983": 0, "459150": 0, "451980": 0, "459149": 0, "451981": 0, "459148": 0, "451978": 0, "459147": 0, "451979": 0, "459146": 0, "451976": 14, "459145": 0, "451977": 0, "459144": 0, "454038": 0, "454039": 0, "454036": 0, "454037": 0, "454034": 0, "454035": 0, "454032": 0, "451984": 0, "459153": 0, "454033": 0, "459152": 0, "463518": 0, "475290": 4, "475289": 6, "461511": 0, "461510": 0, "461509": 0, "461508": 0, "461507": 0, "461516": 0, "461515": 0, "461514": 0, "461513": 0, "461512": 0, }; $(".referee-response-container,.js-referee-report").each(function(index, el) { var reportId = $(el).attr("data-reportid"), reportCount = reportIds[reportId] || 0; $(el).find(".comments-count-container,.js-referee-report-views").html(reportCount); }); var uuidInput = $("#article_uuid"), oldUUId = uuidInput.val(), newUUId = "f135adfe-9fea-42a7-b274-d1056a9c9367"; uuidInput.val(newUUId); $("a[href*='article_uuid=']").each(function(index, el) { var newHref = $(el).attr("href").replace(oldUUId, newUUId); $(el).attr("href", newHref); }); }); An innovative open access publishing platform offering rapid publication and open peer review, whilst supporting data deposition and sharing. Browse Gateways Collections How it Works Contact For Developers Cookie Notice Privacy Notice RSS Submit Your Research Follow us © 2012-2026 F1000 Research Ltd. ISSN 2046-1402 | Legal | Partner of Research4Life • CrossRef • ORCID • FAIRSharing R.templateTests.simpleTemplate = R.template(' $text $text $text $text $text '); R.templateTests.runTests(); var F1000platform = new F1000.Platform({ name: "f1000research", displayName: "F1000Research", hostName: "f1000research.com", id: "1", editorialEmail: "[email protected]", infoEmail: "[email protected]", usePmcStats: true }); $(function(){R.ui.dropdowns('.dropdown-for-authors, .dropdown-for-about, .dropdown-for-myresearch');}); // $(function(){R.ui.dropdowns('.dropdown-for-referees');}); $(document).ready(function () { if ($(".cookie-warning").is(":visible")) { $(".sticky").css("margin-bottom", "35px"); $(".devices").addClass("devices-and-cookie-warning"); } $(".cookie-warning .close-button").click(function (e) { $(".devices").removeClass("devices-and-cookie-warning"); $(".sticky").css("margin-bottom", "0"); }); $("#tweeter-feed .tweet-message").each(function (i, message) { var self = $(message); self.html(linkify(self.html())); }); $(".partner").on("mouseenter mouseleave", function() { $(this).find(".gray-scale, .colour").toggleClass("is-hidden"); }); }); Sign In Remember me Forgotten your password? Sign In Cancel Email or password not correct. Please try again Please wait... $(function(){ // Note: All the setup needs to run against a name attribute and *not* the id due the clonish // nature of facebox... $("a[id=googleSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("GOOGLE"); $("form[id=oAuthForm]").submit(); }); $("a[id=facebookSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("FACEBOOK"); $("form[id=oAuthForm]").submit(); }); $("a[id=orcidSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("ORCID"); $("form[id=oAuthForm]").submit(); }); }); If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here . If you still need help with your Google account password, please click here . You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here . If you still need help with your Facebook account password, please click here . Code not correct, please try again Reset password Cancel Email us for further assistance. Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait... Register $(document).ready(function () { signIn.createSignInAsRow($("#sign-in-form-gfb-popup")); $(".target-field").each(function () { var uris = $(this).val().split("/"); if (uris.pop() === "login") { $(this).val(uris.toString().replace(",","/")); } }); });