Association between aqueous humor MMP-3 levels and varicella zoster virus-induced acute retinal necrosis

Association between aqueous humor MMP-3 levels and varicella zoster virus-induced acute retinal necrosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (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;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Association between aqueous humor MMP-3 levels and varicella zoster virus-induced acute retinal necrosis Zhujian Wang, yu liu, Min Zhou, Boya Lei, Zhujian Wang, Chang Qing This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3452034/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective This study aims to investigate the correlation between matrix metalloproteinase-3 (MMP-3) levels in the aqueous humor and the development of varicella-zoster virus-induced acute retinal necrosis (ARN). Methods Twenty eyes in 20 patients diagnosed with ARN were enrolled, with all the medical records retrospectively reviewed. Aqueous humor samples were collected before the initial antiviral treatments, and MMP-3 levels were quan­tified using immunoturbidimetry. Controls consisted of fifteen eyes from age-related cataract (ARC) patients. Correla­tions between aqueous humor MMP-3 levels and ophthalmic examination results were analyzed using Spearman's cor­relation test. Results MMP-3 were significantly higher in the aqueous humor of ARN patients compared to the controls. ( P <0.001). The following correlations for aqueous humor MMP-3 levels were observed: A low negative correlation with BCVA was observed ( r =-0.447, P =0.0483). A moderate positive correlation was found with the percentage of active retinal necrosis area ( r =0.773, P =0.0001). A moderate negative correlation was identified with vitreous haze ( r = -0.642, P = 0.0023). No significant correlation was found between MMP-3 levels and intraocular pressure or disease duration ( P >0.05). The risk of retinal detachment (RD) was predicted by high MMP-3 levels (HR=4.473; 95% CI, 1.143-17.50; P=0.0314). Conclusion It is suggested by our findings that MMP-3 may play a crucial role in the pathogenesis of ARN, and the detection of aqueous humor MMP-3 is deemed to hold clinical value for both the treatment and prognosis of ARN. Acute retinal necrosis syndrome Metalloproteinase-3 Aqueous humor Figures Figure 1 Figure 2 Key Message What was known before: MMPs play a pivotal role in various ophthalmic diseases Basal MMPs expression upregulated in endothelial cells and immune cells in response to inflammation. What this study adds: MMP-3 levels in varicella-zoster virus-induced ARN aqueous humor was significantly higher than observed in controls. MMP-3 levels in aqueous humor was correlated with the severity of ARN. Aqueous humor MMP-3 levels can serve as a marker for evaluating the severity and prognosis of ARN, shedding light on aspects of ARN pathology Introduction Acute retinal necrosis (ARN) is one of the most serious infectious ocular disease characterized by necrotizing retinitis, occlusive retinal vasculitis, and vitritis, often resulting in severe vision impairment. ARN cases are associated with a higher incidence of retinal detachment (RD), leading to unfavorable visual outcomes. ARN can manifest at any age, most commonly between 15 to 75 years old, with no significant gender differences. While it typically affects one eye, bilateral involvement can also occur [ 1 ] . The most common causative pathogen for ARN is the Varicella-zoster virus (VZV). The pathogenesis of ARN involves intricate interactions between the virus and the host's immune cells and cytokines. However, the specific mechanisms underlying these interactions require further elucidation. Furthermore, the presence of vitreous opacities can hinder fundus examination in certain cases, and the subjectivity in physical examination results underscores the clinical need for laboratory biomarkers in intraocular fluids. Such biomarkers would provide a more accurate assessment of disease severity and treatment efficacy in ARN. Matrix metalloproteinases (MMPs) constitute a family of metal ion-dependent endopeptidases capable of degrading nearly all extracellular matrix (ECM) components, including various collagens and proteins. They play a pivotal role in tissue remodeling during inflammatory and other pathological processes [ 2 ] . MMPs are known to be upregulated in intraocular endothelial cells and immune cells in response to various pathological events such as inflammation and angiogenesis [ 3 , 4 ] . Nevertheless, there remains a paucity of studies investigating the expression of MMPs in ARN. In the current study, we quantitatively assessed the presence of MMP-3 in the aqueous humor of ARN patients, using age-related cataract patients (ARC) as a control group. Our aim was to explore the expression of MMP-3 and its potential correlation with clinical manifestations in ARN patients. Methods Diagnosis criteria and data compilation This retrospective observational study involved an examination of the clinical records of 20 patients (14 men and 6 women) diagnosed with ARN, who visited our clinic between December 2018 and November 2019. All patients met the ARN diagnostic criteria established by the American Uveitis Society [ 5 ] . The causative pathogen was confirmed as VZV by real time PCR of aqueous humor. All patients were followed up for a maximum of 12 months from the initiation of treatment, with follow-up discontinued upon retinal detachment (RD) occurrence. The mean age of the ARN group was 49.0 ± 10.4 years, ranging from 26 to 71 years. The control group consisted of 15 eyes from 15 ARC patients, including 9 males and 6 females, aged 53–77 years, with an average age of 64.2 ± 6.8 years. There were no statistically significant differences in age or gender distribution between the ARN group and the control group ( P > 0.05), indicating comparability between the two groups. This study adhered to the principles of the Declaration of Helsinki and received approval from the Institutional Review Board of the Eye and ENT Hospital of Fudan University. Best corrected visual acuity (BCVA) and ultra-widefield (UWF) fundus imaging were performed for the affected eyes. UWF imaging was conducted using the Optos 200Tx laser scanning ophthalmoscope retinal imaging system (Optos, UK). Two experienced physicians assessed and graded the UWF images to reach a consensus on the percentage of the active retinal necrosis area and the degree of vitreous haze. Additionally, parameters such as duration of disease and intraocular pressure (IOP) were recorded. Sample collection and analysis Once diagnosed, all the patients were treated with timely and unified antiviral therapy. Aqueous humor (100 µl) was extracted before the first injections of ganciclovir. The aqueous humor samples were frozen and stored at -80°C along with the control group samples. The MMP-3 levels in aqueous humor were measured using latex immuno-turbidimetry with commercially available kits purchased from Precise Biotechnology Co., Ltd. (Suzhou, China). Automatic biochemical analyzer (Cobas 8000, Roche, Switzerland) was used for detection. Statistical analyses Continuous data are described as means ± standard deviations, and non-normally distributed data were expressed as median (interquartile range). Independent sample t-test was used for comparisons between groups. Spearman's test was used for correlation coefficient analysis, with r indicating the correlation coefficient. | r |≥0.8 indicates high correlation, 0.5–0.8 moderate correlation, 0.3–0.5 low correlation, and < 0.3 no correlation. Logistic regression analysis was performed to assess the presence of an independent association between aqueous humor MMP-3 and the risk of RD. Kaplan-Meier method, log-rank test were used to analyze time-to-event data. P < 0.05 was considered statistically significant. Results The concentration of MMP-3 in the aqueous humor before treatment was 66.3 ± 43.3 ng/mL, with a median value of 58.85 ng/mL, whereas the control group had a concentration of 3.9 ± 2.7 ng/mL, which was significantly lower than that of the ARN group ( P < 0.001). Figure 1 illustrates the comparison of MMP-3 levels between the two groups. Spearman correlation analysis was performed to evaluate the relationship between aqueous humor MMP-3 levels and ophthalmic parameters in ARN patients. Aqueous humor MMP-3 showed a low negative correlation with BCVA ( P = 0.0483) and a moderate positive correlation with the percentage of the active retinal necrosis area ( P = 0.0001). However, no significant correlation was found between aqueous humor MMP-3 and intraocular pressure or disease duration ( P > 0.05). Ophthalmic parameters and the correlation analysis between aqueous humor MMP-3 levels are presented in Table 2. Vitreous opacities were classified into grades 1–4 based on the clarity of the retinal vessels, with higher grades indicating better clarity. A moderate negative correlation was observed between the grade and levels of MMP-3 in the aqueous humor samples ( r =-0.642, P = 0.0023). Table 1 Ophthalmic parameters and correlation analysis with aqueous humor MMP-3 levels in ARN patients Item Parameter Correlation Coefficient P -value BCVA 0.175(0.12 ~ 0.45) -0.447 0.0483 IOP (mmHg) 13.1 ± 4.8 -0.310 0.8969 Disease duration (days) 16.1 ± 5.4 0.240 0.3087 Percentage of active retinal necrosis area (%) 27.76 ± 20.83 0.773 0.0001 Adjusted for age and sex, aqueous humor MMP-3 level was the independent factor for predicting the risk of RD (OR 1.080 [95% CI, 1.009–1.156], P = 0.028). In terms of RD-free survival, Kaplan–Meier curve showed a significant correlation between aqueous humor MMP-3 levels and the risk of RD (Fig. 2 ; P = 0.0314), with a hazard ratio (HR) of 4.473 (95% CI, 1.143–17.50). Discussion In this study, we utilized an immunoturbidimetric assay to quantify MMP-3 levels in the aqueous humor of ARN patients and monitored changes from initial to final sampling. Our results revealed that the initial MMP-3 levels in the aqueous humor of ARN patients were significantly higher than those of the control group. Further correlation analysis demonstrated a clear association between aqueous humor MMP-3 levels and ophthalmic parameters, showed that aqueous humor MMP-3 levels were associated with the severity of ARN. MMPs play a pivotal role in various ophthalmic diseases, primarily regulating physiological and pathological processes in the eye, such as inflammation, wound healing, angiogenesis, and tumor metastasis. Previous studies have reported that basal MMPs expression is absent or low in normal tissue [ 6 ] , but becomes upregulated in endothelial cells and immune cells in response to inflammation [ 7 ] . Recent research has shown an increase in active MMP-9 levels in aqueous humor samples from neovascular AMD patients compared to control subjects [ 8 ] , and MMP-3 was overexpressed in various virus-induced diseases [ 9 , 10 ] . However, there are few studies on the expression of MMP-3 in the aqueous humor of ARN patients. Our quantitative analysis conducted on a larger sample size, revealed that MMP-3 levels in ARN aqueous humor was 66.3 ± 43.3 ng/mL, significantly higher than the 3.9 ± 2.7 ng/mL observed in controls. This finding further corroborates the heightened expression of MMP-3 in ARN patients and suggests a potential pivotal role for MMP-3 in ARN pathogenesis. The main clinical manifestations of ARN are inflammation or necrosis of the vitreous and retina. The degradation and remodeling of the ECM are crucial pathological processes during the inflammatory response and healing of the retina and vitreous. An imbalance in the ECM leads to the activation of MMPs. Some studies have indicated an increase in the expression of MMP-2 and MMP-9 in aqueous humor at one week, reaching peak levels during the height of inflammation in a rat model of experimental uveitis [ 11 ] . The larger area of retinal necrosis and the stronger inflammatory response in ARN patients, leading to increased infiltration of inflammatory cells, including microglia. Microglia are considered the primary source of MMPs in retinal tissues [ 12 ] . Therefore, the significant correlation observed in this study between aqueous humor MMP-3 levels and the severity of ARN may be attributed to the migration of activated microglia to lesion sites and the subsequent increase in MMP-3 expression [ 13 ] . The vitreous humor primarily consists of collagen and glycosaminoglycans and the vascular wall of the retina is mainly composed of type IV collagen [14]. MMPs are unique proteinases capable of hydrolyzing fibrous collagen, enabling extensive degradation of the ECM and intact type IV collagen basement membranes. Activated MMP-3 can interact with ECM proteins such as fibronectin (FN) and laminin (LN) in the retina [ 15 ] , subsequently activating other MMPs to collectively participate in ECM degradation. Previous studies have observed elevated levels of stromelysin-1 (MMP-3) in vitreous and subretinal fluid during rhegmatogenous retinal detachment (RRD) [ 16 , 17 ] , where it served as a potential indicator of RRD extent. In our current investigation, the level of MMP-3 in the aqueous humor emerged as a predictor for the risk of RD. This finding suggests that the disruption of MMPs homeostasis may play a crucial role in creating a permissive environment for RD. These discoveries offer fresh insights into the potential mechanisms underlying RD and may prove valuable in developing protective measures for patients with ARN. It's important to acknowledge several limitations in this study. Firstly, the small sample size was due to strict inclusion criteria. Secondly, we measured total MMP-3 levels rather than overall enzymatic activity in aqueous humor, limiting us to suggesting an association between aqueous humor MMP-3 levels and ARN disease presentation. To address these limitations, we plan to expand our study to include more cases and extend the follow-up period, allowing for a deeper investigation into the role of MMP-3 in ARN pathogenesis. Conclusion Our findings suggest that aqueous humor MMP-3 levels can serve as a marker for evaluating the severity and prognosis of ARN, shedding light on aspects of ARN pathology. Further exploration of the role played by MMPs molecules in the disease processes of ARN patients may offer novel insights and directions for disease treatment and intervention. References Meghpara B, Sulkowski G, Kesen MR, Tessler HH, Goldstein DA. Long-term follow-up of acute retinal necrosis. Retina (Philadelphia, Pa). 2010;30(5):795-800. Epub 2010/01/09. doi: 10.1097/IAE.0b013e3181c7013c. PubMed PMID: 20057342. Nagase H, Woessner JF, Jr. Matrix metalloproteinases. The Journal of biological chemistry. 1999;274(31):21491-4. Epub 1999/07/27. doi: 10.1074/jbc.274.31.21491. PubMed PMID: 10419448. Lambert V, Munaut C, Jost M, Noël A, Werb Z, Foidart JM, et al. Matrix metalloproteinase-9 contributes to choroidal neovascularization. The American journal of pathology. 2002;161(4):1247-53. Epub 2002/10/09. doi: 10.1016/s0002-9440(10)64401-x. PubMed PMID: 12368198; PubMed Central PMCID: PMCPMC1867305. Giebel SJ, Menicucci G, McGuire PG, Das A. Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood-retinal barrier. Laboratory investigation; a journal of technical methods and pathology. 2005;85(5):597-607. Epub 2005/02/16. doi: 10.1038/labinvest.3700251. PubMed PMID: 15711567. Holland GN. Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society. American journal of ophthalmology. 1994;117(5):663-7. Epub 1994/05/15. doi: 10.1016/s0002-9394(14)70075-3. PubMed PMID: 8172275. Pepper MS. Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arteriosclerosis, thrombosis, and vascular biology. 2001;21(7):1104-17. Epub 2001/07/14. doi: 10.1161/hq0701.093685. PubMed PMID: 11451738. Lambert V, Wielockx B, Munaut C, Galopin C, Jost M, Itoh T, et al. MMP-2 and MMP-9 synergize in promoting choroidal neovascularization. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2003;17(15):2290-2. Epub 2003/10/18. doi: 10.1096/fj.03-0113fje. PubMed PMID: 14563686. Kim J, Kim JH, Do JY, Lee JY, Yanai R, Lee IK, et al. Key Role of Microglial Matrix Metalloproteinases in Choroidal Neovascularization. Frontiers in cellular neuroscience. 2021;15:638098. Epub 2021/03/16. doi: 10.3389/fncel.2021.638098. PubMed PMID: 33716674; PubMed Central PMCID: PMCPMC7954091. Filiberti A, Gmyrek GB, Berube AN, Royer DJ, Carr DJJ. An intact complement system dampens cornea inflammation during acute primary HSV-1 infection. Scientific reports. 2021;11(1):10247. Epub 2021/05/15. doi: 10.1038/s41598-021-89818-9. PubMed PMID: 33986436; PubMed Central PMCID: PMCPMC8119410. Sengupta S, Addya S, Biswas D, Banerjee P, Sarma JD. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in murine β-coronavirus-induced neuroinflammation. Virology. 2022;566:122-35. Epub 2021/12/16. doi: 10.1016/j.virol.2021.11.012. PubMed PMID: 34906793; PubMed Central PMCID: PMCPMC8648396. Cuello C, Wakefield D, Di Girolamo N. Neutrophil accumulation correlates with type IV collagenase/gelatinase activity in endotoxin induced uveitis. The British journal of ophthalmology. 2002;86(3):290-5. Epub 2002/02/28. doi: 10.1136/bjo.86.3.290. PubMed PMID: 11864886; PubMed Central PMCID: PMCPMC1771059. Chen M, Xu H. Parainflammation, chronic inflammation, and age-related macular degeneration. Journal of leukocyte biology. 2015;98(5):713-25. Epub 2015/08/22. doi: 10.1189/jlb.3RI0615-239R. PubMed PMID: 26292978; PubMed Central PMCID: PMCPMC4733662. Karlstetter M, Scholz R, Rutar M, Wong WT, Provis JM, Langmann T. Retinal microglia: just bystander or target for therapy? Progress in retinal and eye research. 2015;45:30-57. Epub 2014/12/06. doi: 10.1016/j.preteyeres.2014.11.004. PubMed PMID: 25476242. Azuma N, Tajima S, Konomi H, Hida T, Akiya S, Uemura Y. Glycosaminoglycan and collagen distribution in the developing human vitreous. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 1998;236(9):679-87. Epub 1998/10/23. doi: 10.1007/s004170050141. PubMed PMID: 9782429. Ocklind A. Effect of latanoprost on the extracellular matrix of the ciliary muscle. A study on cultured cells and tissue sections. Experimental eye research. 1998;67(2):179-91. Epub 1998/09/12. doi: 10.1006/exer.1998.0508. PubMed PMID: 9733584. Symeonidis C, Diza E, Papakonstantinou E, Souliou E, Karakiulakis G, Dimitrakos SA. Expression of matrix metalloproteinases in the subretinal fluid correlates with the extent of rhegmatogenous retinal detachment. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2007;245(4):560-8. Epub 2006/08/31. doi: 10.1007/s00417-006-0386-3. PubMed PMID: 16941143. Symeonidis C, Papakonstantinou E, Souliou E, Karakiulakis G, Dimitrakos SA, Diza E. Correlation of matrix metalloproteinase levels with the grade of proliferative vitreoretinopathy in the subretinal fluid and vitreous during rhegmatogenous retinal detachment. Acta ophthalmologica. 2011;89(4):339-45. Epub 2009/09/22. doi: 10.1111/j.1755-3768.2009.01701.x. PubMed PMID: 19764916. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3452034","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":244456166,"identity":"2e591c0f-d59f-406b-976c-9e735b4e8b2c","order_by":0,"name":"Zhujian 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patients.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3452034/v1/7aeeb28ef9c90ae5825c66e6.png"},{"id":54164972,"identity":"77f720d3-4097-4481-a3c4-22fcdef7e176","added_by":"auto","created_at":"2024-04-05 13:26:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":106921,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier estimates of RD-free survival according to the MMP-3 level in aqueous humor.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3452034/v1/3a0c4053479dba83ff88c769.png"},{"id":58046249,"identity":"0a86e282-3e1c-44de-b7db-6a2290926143","added_by":"auto","created_at":"2024-06-10 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was significantly higher than observed in controls.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMMP-3 levels in aqueous humor\u0026nbsp;was correlated with the severity of ARN.\u003c/li\u003e\n \u003cli\u003eAqueous humor MMP-3 levels can serve as a marker for evaluating the severity and prognosis of ARN, shedding light on aspects of ARN pathology\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eAcute retinal necrosis (ARN) is one of the most serious infectious ocular disease characterized by necrotizing retinitis, occlusive retinal vasculitis, and vitritis, often resulting in severe vision impairment. ARN cases are associated with a higher incidence of retinal detachment (RD), leading to unfavorable visual outcomes. ARN can manifest at any age, most commonly between 15 to 75 years old, with no significant gender differences. While it typically affects one eye, bilateral involvement can also occur \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. The most common causative pathogen for ARN is the Varicella-zoster virus (VZV). The pathogenesis of ARN involves intricate interactions between the virus and the host's immune cells and cytokines. However, the specific mechanisms underlying these interactions require further elucidation. Furthermore, the presence of vitreous opacities can hinder fundus examination in certain cases, and the subjectivity in physical examination results underscores the clinical need for laboratory biomarkers in intraocular fluids. Such biomarkers would provide a more accurate assessment of disease severity and treatment efficacy in ARN.\u003c/p\u003e \u003cp\u003eMatrix metalloproteinases (MMPs) constitute a family of metal ion-dependent endopeptidases capable of degrading nearly all extracellular matrix (ECM) components, including various collagens and proteins. They play a pivotal role in tissue remodeling during inflammatory and other pathological processes \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. MMPs are known to be upregulated in intraocular endothelial cells and immune cells in response to various pathological events such as inflammation and angiogenesis \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Nevertheless, there remains a paucity of studies investigating the expression of MMPs in ARN. In the current study, we quantitatively assessed the presence of MMP-3 in the aqueous humor of ARN patients, using age-related cataract patients (ARC) as a control group. Our aim was to explore the expression of MMP-3 and its potential correlation with clinical manifestations in ARN patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDiagnosis criteria and data compilation\u003c/h2\u003e \u003cp\u003eThis retrospective observational study involved an examination of the clinical records of 20 patients (14 men and 6 women) diagnosed with ARN, who visited our clinic between December 2018 and November 2019. All patients met the ARN diagnostic criteria established by the American Uveitis Society \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. The causative pathogen was confirmed as VZV by real time PCR of aqueous humor. All patients were followed up for a maximum of 12 months from the initiation of treatment, with follow-up discontinued upon retinal detachment (RD) occurrence. The mean age of the ARN group was 49.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.4 years, ranging from 26 to 71 years. The control group consisted of 15 eyes from 15 ARC patients, including 9 males and 6 females, aged 53\u0026ndash;77 years, with an average age of 64.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8 years. There were no statistically significant differences in age or gender distribution between the ARN group and the control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), indicating comparability between the two groups. This study adhered to the principles of the Declaration of Helsinki and received approval from the Institutional Review Board of the Eye and ENT Hospital of Fudan University.\u003c/p\u003e \u003cp\u003eBest corrected visual acuity (BCVA) and ultra-widefield (UWF) fundus imaging were performed for the affected eyes. UWF imaging was conducted using the Optos 200Tx laser scanning ophthalmoscope retinal imaging system (Optos, UK). Two experienced physicians assessed and graded the UWF images to reach a consensus on the percentage of the active retinal necrosis area and the degree of vitreous haze. Additionally, parameters such as duration of disease and intraocular pressure (IOP) were recorded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSample collection and analysis\u003c/h2\u003e \u003cp\u003eOnce diagnosed, all the patients were treated with timely and unified antiviral therapy. Aqueous humor (100 \u0026micro;l) was extracted before the first injections of ganciclovir. The aqueous humor samples were frozen and stored at -80\u0026deg;C along with the control group samples. The MMP-3 levels in aqueous humor were measured using latex immuno-turbidimetry with commercially available kits purchased from Precise Biotechnology Co., Ltd. (Suzhou, China). Automatic biochemical analyzer (Cobas 8000, Roche, Switzerland) was used for detection.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eContinuous data are described as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations, and non-normally distributed data were expressed as median (interquartile range). Independent sample t-test was used for comparisons between groups. Spearman's test was used for correlation coefficient analysis, with r indicating the correlation coefficient. |\u003cem\u003er\u003c/em\u003e|\u0026ge;0.8 indicates high correlation, 0.5\u0026ndash;0.8 moderate correlation, 0.3\u0026ndash;0.5 low correlation, and \u0026lt;\u0026thinsp;0.3 no correlation. Logistic regression analysis was performed to assess the presence of an independent association between aqueous humor MMP-3 and the risk of RD. Kaplan-Meier method, log-rank test were used to analyze time-to-event data. \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe concentration of MMP-3 in the aqueous humor before treatment was 66.3\u0026thinsp;\u0026plusmn;\u0026thinsp;43.3 ng/mL, with a median value of 58.85 ng/mL, whereas the control group had a concentration of 3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7 ng/mL, which was significantly lower than that of the ARN group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates the comparison of MMP-3 levels between the two groups.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSpearman correlation analysis was performed to evaluate the relationship between aqueous humor MMP-3 levels and ophthalmic parameters in ARN patients. Aqueous humor MMP-3 showed a low negative correlation with BCVA (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0483) and a moderate positive correlation with the percentage of the active retinal necrosis area (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001). However, no significant correlation was found between aqueous humor MMP-3 and intraocular pressure or disease duration (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Ophthalmic parameters and the correlation analysis between aqueous humor MMP-3 levels are presented in Table\u0026nbsp;2. Vitreous opacities were classified into grades 1\u0026ndash;4 based on the clarity of the retinal vessels, with higher grades indicating better clarity. A moderate negative correlation was observed between the grade and levels of MMP-3 in the aqueous humor samples (\u003cem\u003er\u003c/em\u003e=-0.642, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0023).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOphthalmic parameters and correlation analysis with aqueous humor MMP-3 levels in ARN patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eItem\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCorrelation Coefficient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.175(0.12\u0026thinsp;~\u0026thinsp;0.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.447\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0483\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIOP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.310\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.8969\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease duration (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.240\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3087\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePercentage of active retinal necrosis area (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27.76\u0026thinsp;\u0026plusmn;\u0026thinsp;20.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.773\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAdjusted for age and sex, aqueous humor MMP-3 level was the independent factor for predicting the risk of RD (OR 1.080 [95% CI, 1.009\u0026ndash;1.156], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028). In terms of RD-free survival, Kaplan\u0026ndash;Meier curve showed a significant correlation between aqueous humor MMP-3 levels and the risk of RD (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0314), with a hazard ratio (HR) of 4.473 (95% CI, 1.143\u0026ndash;17.50).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we utilized an immunoturbidimetric assay to quantify MMP-3 levels in the aqueous humor of ARN patients and monitored changes from initial to final sampling. Our results revealed that the initial MMP-3 levels in the aqueous humor of ARN patients were significantly higher than those of the control group. Further correlation analysis demonstrated a clear association between aqueous humor MMP-3 levels and ophthalmic parameters, showed that aqueous humor MMP-3 levels were associated with the severity of ARN.\u003c/p\u003e \u003cp\u003eMMPs play a pivotal role in various ophthalmic diseases, primarily regulating physiological and pathological processes in the eye, such as inflammation, wound healing, angiogenesis, and tumor metastasis. Previous studies have reported that basal MMPs expression is absent or low in normal tissue \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e, but becomes upregulated in endothelial cells and immune cells in response to inflammation \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Recent research has shown an increase in active MMP-9 levels in aqueous humor samples from neovascular AMD patients compared to control subjects \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, and MMP-3 was overexpressed in various virus-induced diseases \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. However, there are few studies on the expression of MMP-3 in the aqueous humor of ARN patients. Our quantitative analysis conducted on a larger sample size, revealed that MMP-3 levels in ARN aqueous humor was 66.3\u0026thinsp;\u0026plusmn;\u0026thinsp;43.3 ng/mL, significantly higher than the 3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7 ng/mL observed in controls. This finding further corroborates the heightened expression of MMP-3 in ARN patients and suggests a potential pivotal role for MMP-3 in ARN pathogenesis.\u003c/p\u003e \u003cp\u003eThe main clinical manifestations of ARN are inflammation or necrosis of the vitreous and retina. The degradation and remodeling of the ECM are crucial pathological processes during the inflammatory response and healing of the retina and vitreous. An imbalance in the ECM leads to the activation of MMPs. Some studies have indicated an increase in the expression of MMP-2 and MMP-9 in aqueous humor at one week, reaching peak levels during the height of inflammation in a rat model of experimental uveitis \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. The larger area of retinal necrosis and the stronger inflammatory response in ARN patients, leading to increased infiltration of inflammatory cells, including microglia. Microglia are considered the primary source of MMPs in retinal tissues \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Therefore, the significant correlation observed in this study between aqueous humor MMP-3 levels and the severity of ARN may be attributed to the migration of activated microglia to lesion sites and the subsequent increase in MMP-3 expression \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe vitreous humor primarily consists of collagen and glycosaminoglycans and the vascular wall of the retina is mainly composed of type IV collagen [14]. MMPs are unique proteinases capable of hydrolyzing fibrous collagen, enabling extensive degradation of the ECM and intact type IV collagen basement membranes. Activated MMP-3 can interact with ECM proteins such as fibronectin (FN) and laminin (LN) in the retina \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, subsequently activating other MMPs to collectively participate in ECM degradation. Previous studies have observed elevated levels of stromelysin-1 (MMP-3) in vitreous and subretinal fluid during rhegmatogenous retinal detachment (RRD) \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e, where it served as a potential indicator of RRD extent. In our current investigation, the level of MMP-3 in the aqueous humor emerged as a predictor for the risk of RD. This finding suggests that the disruption of MMPs homeostasis may play a crucial role in creating a permissive environment for RD. These discoveries offer fresh insights into the potential mechanisms underlying RD and may prove valuable in developing protective measures for patients with ARN.\u003c/p\u003e \u003cp\u003eIt's important to acknowledge several limitations in this study. Firstly, the small sample size was due to strict inclusion criteria. Secondly, we measured total MMP-3 levels rather than overall enzymatic activity in aqueous humor, limiting us to suggesting an association between aqueous humor MMP-3 levels and ARN disease presentation. To address these limitations, we plan to expand our study to include more cases and extend the follow-up period, allowing for a deeper investigation into the role of MMP-3 in ARN pathogenesis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur findings suggest that aqueous humor MMP-3 levels can serve as a marker for evaluating the severity and prognosis of ARN, shedding light on aspects of ARN pathology. Further exploration of the role played by MMPs molecules in the disease processes of ARN patients may offer novel insights and directions for disease treatment and intervention.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMeghpara B, Sulkowski G, Kesen MR, Tessler HH, Goldstein DA. Long-term follow-up of acute retinal necrosis. Retina (Philadelphia, Pa). 2010;30(5):795-800. Epub 2010/01/09. doi: 10.1097/IAE.0b013e3181c7013c. PubMed PMID: 20057342.\u003c/li\u003e\n\u003cli\u003eNagase H, Woessner JF, Jr. Matrix metalloproteinases. The Journal of biological chemistry. 1999;274(31):21491-4. Epub 1999/07/27. doi: 10.1074/jbc.274.31.21491. PubMed PMID: 10419448.\u003c/li\u003e\n\u003cli\u003eLambert V, Munaut C, Jost M, No\u0026euml;l A, Werb Z, Foidart JM, et al. Matrix metalloproteinase-9 contributes to choroidal neovascularization. The American journal of pathology. 2002;161(4):1247-53. Epub 2002/10/09. doi: 10.1016/s0002-9440(10)64401-x. PubMed PMID: 12368198; PubMed Central PMCID: PMCPMC1867305.\u003c/li\u003e\n\u003cli\u003eGiebel SJ, Menicucci G, McGuire PG, Das A. Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood-retinal barrier. Laboratory investigation; a journal of technical methods and pathology. 2005;85(5):597-607. Epub 2005/02/16. doi: 10.1038/labinvest.3700251. PubMed PMID: 15711567.\u003c/li\u003e\n\u003cli\u003eHolland GN. Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society. American journal of ophthalmology. 1994;117(5):663-7. Epub 1994/05/15. doi: 10.1016/s0002-9394(14)70075-3. PubMed PMID: 8172275.\u003c/li\u003e\n\u003cli\u003ePepper MS. Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arteriosclerosis, thrombosis, and vascular biology. 2001;21(7):1104-17. Epub 2001/07/14. doi: 10.1161/hq0701.093685. PubMed PMID: 11451738.\u003c/li\u003e\n\u003cli\u003eLambert V, Wielockx B, Munaut C, Galopin C, Jost M, Itoh T, et al. MMP-2 and MMP-9 synergize in promoting choroidal neovascularization. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2003;17(15):2290-2. Epub 2003/10/18. doi: 10.1096/fj.03-0113fje. PubMed PMID: 14563686.\u003c/li\u003e\n\u003cli\u003eKim J, Kim JH, Do JY, Lee JY, Yanai R, Lee IK, et al. Key Role of Microglial Matrix Metalloproteinases in Choroidal Neovascularization. Frontiers in cellular neuroscience. 2021;15:638098. Epub 2021/03/16. doi: 10.3389/fncel.2021.638098. PubMed PMID: 33716674; PubMed Central PMCID: PMCPMC7954091.\u003c/li\u003e\n\u003cli\u003eFiliberti A, Gmyrek GB, Berube AN, Royer DJ, Carr DJJ. An intact complement system dampens cornea inflammation during acute primary HSV-1 infection. Scientific reports. 2021;11(1):10247. Epub 2021/05/15. doi: 10.1038/s41598-021-89818-9. PubMed PMID: 33986436; PubMed Central PMCID: PMCPMC8119410.\u003c/li\u003e\n\u003cli\u003eSengupta S, Addya S, Biswas D, Banerjee P, Sarma JD. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in murine \u0026beta;-coronavirus-induced neuroinflammation. Virology. 2022;566:122-35. Epub 2021/12/16. doi: 10.1016/j.virol.2021.11.012. PubMed PMID: 34906793; PubMed Central PMCID: PMCPMC8648396.\u003c/li\u003e\n\u003cli\u003eCuello C, Wakefield D, Di Girolamo N. Neutrophil accumulation correlates with type IV collagenase/gelatinase activity in endotoxin induced uveitis. The British journal of ophthalmology. 2002;86(3):290-5. Epub 2002/02/28. doi: 10.1136/bjo.86.3.290. PubMed PMID: 11864886; PubMed Central PMCID: PMCPMC1771059.\u003c/li\u003e\n\u003cli\u003eChen M, Xu H. Parainflammation, chronic inflammation, and age-related macular degeneration. Journal of leukocyte biology. 2015;98(5):713-25. Epub 2015/08/22. doi: 10.1189/jlb.3RI0615-239R. PubMed PMID: 26292978; PubMed Central PMCID: PMCPMC4733662.\u003c/li\u003e\n\u003cli\u003eKarlstetter M, Scholz R, Rutar M, Wong WT, Provis JM, Langmann T. Retinal microglia: just bystander or target for therapy? Progress in retinal and eye research. 2015;45:30-57. Epub 2014/12/06. doi: 10.1016/j.preteyeres.2014.11.004. PubMed PMID: 25476242.\u003c/li\u003e\n\u003cli\u003eAzuma N, Tajima S, Konomi H, Hida T, Akiya S, Uemura Y. Glycosaminoglycan and collagen distribution in the developing human vitreous. Graefe\u0026apos;s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 1998;236(9):679-87. Epub 1998/10/23. doi: 10.1007/s004170050141. PubMed PMID: 9782429.\u003c/li\u003e\n\u003cli\u003eOcklind A. Effect of latanoprost on the extracellular matrix of the ciliary muscle. A study on cultured cells and tissue sections. Experimental eye research. 1998;67(2):179-91. Epub 1998/09/12. doi: 10.1006/exer.1998.0508. PubMed PMID: 9733584.\u003c/li\u003e\n\u003cli\u003eSymeonidis C, Diza E, Papakonstantinou E, Souliou E, Karakiulakis G, Dimitrakos SA. Expression of matrix metalloproteinases in the subretinal fluid correlates with the extent of rhegmatogenous retinal detachment. Graefe\u0026apos;s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2007;245(4):560-8. Epub 2006/08/31. doi: 10.1007/s00417-006-0386-3. PubMed PMID: 16941143.\u003c/li\u003e\n\u003cli\u003eSymeonidis C, Papakonstantinou E, Souliou E, Karakiulakis G, Dimitrakos SA, Diza E. Correlation of matrix metalloproteinase levels with the grade of proliferative vitreoretinopathy in the subretinal fluid and vitreous during rhegmatogenous retinal detachment. Acta ophthalmologica. 2011;89(4):339-45. Epub 2009/09/22. doi: 10.1111/j.1755-3768.2009.01701.x. PubMed PMID: 19764916.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Acute retinal necrosis syndrome, Metalloproteinase-3, Aqueous humor","lastPublishedDoi":"10.21203/rs.3.rs-3452034/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3452034/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e This study aims to investigate the correlation between matrix metalloproteinase-3 (MMP-3) levels in the aqueous humor and the development of varicella-zoster virus-induced acute retinal necrosis (ARN).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e Twenty eyes in 20 patients diagnosed with ARN were enrolled, with all the medical records retrospectively reviewed. Aqueous humor samples were collected before the initial antiviral treatments, and MMP-3 levels were quan­tified using immunoturbidimetry. Controls consisted of fifteen eyes from age-related cataract (ARC) patients. Correla­tions between aqueous humor MMP-3 levels and ophthalmic examination results were analyzed using Spearman's cor­relation test.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e MMP-3 were significantly higher in the aqueous humor of ARN patients compared to the controls. (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001). The following correlations for aqueous humor MMP-3 levels were observed: A low negative correlation with BCVA was observed (\u003cem\u003er\u003c/em\u003e=-0.447, \u003cem\u003eP\u003c/em\u003e=0.0483). A moderate positive correlation was found with the percentage of active retinal necrosis area (\u003cem\u003er\u003c/em\u003e=0.773, \u003cem\u003eP\u003c/em\u003e=0.0001). A moderate negative correlation was identified with vitreous haze (\u003cem\u003er\u003c/em\u003e= -0.642, \u003cem\u003eP\u003c/em\u003e= 0.0023). No significant correlation was found between MMP-3 levels and intraocular pressure or disease duration (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05). The risk of retinal detachment (RD) was predicted by high MMP-3 levels (HR=4.473; 95% CI, 1.143-17.50; P=0.0314).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e It is suggested by our findings that MMP-3 may play a crucial role in the pathogenesis of ARN, and the detection of aqueous humor MMP-3 is deemed to hold clinical value for both the treatment and prognosis of ARN.\u003c/p\u003e","manuscriptTitle":"Association between aqueous humor MMP-3 levels and varicella zoster virus-induced acute retinal necrosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-05 13:26:46","doi":"10.21203/rs.3.rs-3452034/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"12ec28ce-d18e-46bd-a219-32474e8120f5","owner":[],"postedDate":"April 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-10T11:35:13+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-05 13:26:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3452034","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3452034","identity":"rs-3452034","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}