{"paper_id":"35cedb7a-80c9-48f0-b894-07b5e6b86eaf","body_text":"Optic Nerve Cerebrospinal Fluid Drainage via Lymphatic Vessels in Its Sheath | 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 Optic Nerve Cerebrospinal Fluid Drainage via Lymphatic Vessels in Its Sheath Yang Xu, Wenjing Chen, Yuwei Hu, Huan Wang, Min Yan, Yuan Xie, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7972068/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Cerebrospinal fluid (CSF) surrounding the optic nerve plays a crucial role in nutrient transport, metabolic waste removal, and maintaining normal optic nerve function. Increasing evidence suggests that optic disc edema observed in astronauts during long-duration spaceflight—referred to as Spaceflight Associated Neuro-Ocular Syndrome (SANS)—may result from the retention of optic nerve CSF, a phenomenon likely linked to impaired drainage. However, the specific drainage pathway of optic nerve CSF remains unclear. Given that the optic nerve sheath is an extension of the cranial meninges, we hypothesize that its CSF is drained via lymphatic vessels rather than refluxing back into the cranial cavity. To test this hypothesis, we assessed the pressure relationship between intracranial CSF and optic nerve CSF, and traced its drainage pathway through anatomical and physiological observations. Our results show that the CSF pressure within the optic nerve sheath is consistently lower than intracranial pressure, and no reflux of CSF into the cranial cavity was observed. Instead, optic nerve CSF is drained into the deep cervical lymph nodes via lymphatic vessels within the optic nerve sheath. These findings provide new insights into the physiological turnover and drainage pathways of optic nerve CSF, and may contribute to understanding the pathogenesis of SANS. Health sciences/Diseases Health sciences/Medical research Health sciences/Neurology Biological sciences/Neuroscience lymphatic vessels optic nerve sheath cerebrospinal fluid Spaceflight Associated Neuro-Ocular Syndrome space medicine. Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 07 Feb, 2026 Reviews received at journal 26 Jan, 2026 Reviewers agreed at journal 12 Jan, 2026 Reviews received at journal 02 Jan, 2026 Reviewers agreed at journal 21 Nov, 2025 Reviewers invited by journal 10 Nov, 2025 Editor assigned by journal 05 Nov, 2025 Submission checks completed at journal 04 Nov, 2025 First submitted to journal 28 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-7972068\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":545801426,\"identity\":\"7be738a7-0ba1-440f-ab8b-871f8566e946\",\"order_by\":0,\"name\":\"Yang Xu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Third People's Hospital of Zhangjiagang\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yang\",\"middleName\":\"\",\"lastName\":\"Xu\",\"suffix\":\"\"},{\"id\":545801427,\"identity\":\"ed311cdb-550c-4f7e-abab-56df30b74b20\",\"order_by\":1,\"name\":\"Wenjing 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Sheath\",\"fulltext\":[],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":false,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":true,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":true,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"npj-microgravity\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"npjmgrav\",\"sideBox\":\"Learn more about [npj Microgravity](http://www.nature.com/npjmgrav/)\",\"snPcode\":\"41526\",\"submissionUrl\":\"https://submission.springernature.com/new-submission/41526/3\",\"title\":\"npj Microgravity\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"NPJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"lymphatic vessels, optic nerve sheath, cerebrospinal fluid, Spaceflight Associated Neuro-Ocular Syndrome, space medicine.\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-7972068/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-7972068/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eCerebrospinal fluid (CSF) surrounding the optic nerve plays a crucial role in nutrient transport, metabolic waste removal, and maintaining normal optic nerve function. Increasing evidence suggests that optic disc edema observed in astronauts during long-duration spaceflight\\u0026mdash;referred to as Spaceflight Associated Neuro-Ocular Syndrome (SANS)\\u0026mdash;may result from the retention of optic nerve CSF, a phenomenon likely linked to impaired drainage. However, the specific drainage pathway of optic nerve CSF remains unclear.\\u003c/p\\u003e\\u003cp\\u003eGiven that the optic nerve sheath is an extension of the cranial meninges, we hypothesize that its CSF is drained via lymphatic vessels rather than refluxing back into the cranial cavity. To test this hypothesis, we assessed the pressure relationship between intracranial CSF and optic nerve CSF, and traced its drainage pathway through anatomical and physiological observations.\\u003c/p\\u003e\\u003cp\\u003eOur results show that the CSF pressure within the optic nerve sheath is consistently lower than intracranial pressure, and no reflux of CSF into the cranial cavity was observed. Instead, optic nerve CSF is drained into the deep cervical lymph nodes via lymphatic vessels within the optic nerve sheath.\\u003c/p\\u003e\\u003cp\\u003eThese findings provide new insights into the physiological turnover and drainage pathways of optic nerve CSF, and may contribute to understanding the pathogenesis of SANS.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Optic Nerve Cerebrospinal Fluid Drainage via Lymphatic Vessels in Its Sheath\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-11-19 18:29:45\",\"doi\":\"10.21203/rs.3.rs-7972068/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2026-02-08T01:03:48+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-01-26T13:28:24+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"2944194028296162509810300380816515349\",\"date\":\"2026-01-12T21:01:52+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-01-02T09:42:41+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"20576194857255358708331578888850365269\",\"date\":\"2025-11-21T13:08:20+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2025-11-10T12:36:04+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2025-11-06T01:00:44+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2025-11-05T02:40:50+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"npj Microgravity\",\"date\":\"2025-10-28T14:47:35+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"npj-microgravity\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"npjmgrav\",\"sideBox\":\"Learn more about [npj Microgravity](http://www.nature.com/npjmgrav/)\",\"snPcode\":\"41526\",\"submissionUrl\":\"https://submission.springernature.com/new-submission/41526/3\",\"title\":\"npj Microgravity\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"NPJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"04cc18d8-5c22-4f0f-b348-9443597744bf\",\"owner\":[],\"postedDate\":\"November 19th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"under-review\",\"subjectAreas\":[{\"id\":58065817,\"name\":\"Health sciences/Diseases\"},{\"id\":58065818,\"name\":\"Health sciences/Medical research\"},{\"id\":58065819,\"name\":\"Health sciences/Neurology\"},{\"id\":58065820,\"name\":\"Biological sciences/Neuroscience\"}],\"tags\":[],\"updatedAt\":\"2026-04-25T06:09:14+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-11-19 18:29:45\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-7972068\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-7972068\",\"identity\":\"rs-7972068\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}