Demystifying the feasibility of in vivo nonresonant Raman spectroscopy of the human retina

Demystifying the feasibility of in vivo nonresonant Raman spectroscopy of the human retina | 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 Demystifying the feasibility of in vivo nonresonant Raman spectroscopy of the human retina Rainer Leitgeb, Ryan Sentosa, Milana Kendrisic, Matthias Salas, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3891690/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Mar, 2026 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Abstract Early detection of retinal molecular biomarkers is crucial for addressing the unmet clinical need to prevent irreversible neural tissue damage in ophthalmic and neurodegenerative diseases. Among emerging molecular sensing techniques, non-resonant Raman spectroscopy stands out as a naturally label-free and noninvasive method, offering rich biochemical information. However, in vivo detection of non-resonant Raman spectra from retinal tissue has proven to be challenging so far. Previous studies have reported conflicting results, likely due to overwhelming pigment autofluorescence. In this study, we identified the optic nerve head as the optimal retinal location for acquiring non-resonant Raman spectra in the molecular fingerprint region. Through longitudinal intra-subject measurements, we revealed dynamic changes in the molecular composition. Furthermore, a comparative study across age groups enabled the identification of molecular alterations associated with aging. These findings establish a critical foundation for utilizing non-resonant Raman spectroscopy as an early diagnostic tool for the detection of molecular biomarkers associated with ophthalmic and neurodegenerative diseases. Physical sciences/Optics and photonics/Optical techniques/Optical spectroscopy/Raman spectroscopy Biological sciences/Biological techniques/Imaging/Optical imaging Full Text Additional Declarations Yes there is potential Competing Interest. M.E. and M.Kem. are employed by Carl Zeiss Meditec AG; I.K. was employed by Innolume GmbH; V.S. was employed by HORIBA France SAS; T.S. is employed by Carl Zeiss Meditec, Inc; All other authors declare that they have no competing interests. Supplementary Files NatureCommunicationssupplementarymaterialsSentosaetal.pdf Supplementary Materials NatureCommunicationssupplementarymaterialsSentosaetal.pdf NatCommsuppInfoSentosaetal.docx Supplementary Information Cite Share Download PDF Status: Published Journal Publication published 03 Mar, 2026 Read the published version in Communications Biology → Version 1 posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-3891690","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":443763578,"identity":"b739e8ec-48d1-45aa-b696-add142181734","order_by":0,"name":"Rainer 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