{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:51:18Z","timestamp":1791352278480,"version":"4.3.1"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R00MH120279"],"award-info":[{"award-number":["R00MH120279"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21NS144777"],"award-info":[{"award-number":["R21NS144777"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31NS151910"],"award-info":[{"award-number":["F31NS151910"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005191","name":"Craig H. Neilsen Foundation","doi-asserted-by":"publisher","award":["1348565"],"award-info":[{"award-number":["1348565"]}],"id":[{"id":"10.13039\/100005191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008451","name":"Binghamton University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008451","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Glaucoma is a leading cause of irreversible blindness, yet the circuit\u2010level mechanisms contributing to retinal ganglion cell (RGC) degeneration remain incompletely defined. Although multiple neuroprotective strategies have been explored, clinical translation remains limited. Here, we identify early dysfunction of inner retinal inhibitory circuitry as a modifiable contributor to RGC vulnerability during ocular hypertensive stress. In mouse ocular hypertension models, inner nuclear layer neurons exhibited increased c\u2010fos expression and enhanced oscillatory potential\u2010associated differential electroretinography signals before substantial RGC loss was detected, suggesting early retinal circuit hyperactivity. Broad pharmacological attenuation of GABAergic and glycinergic inhibitory signaling improved RGC survival without reducing intraocular pressure, supporting a functional contribution of inhibitory neurotransmission to RGC vulnerability. Moreover, Cre\u2010dependent AAV delivery of Lin28, an RNA\u2010binding regulator of post\u2010transcriptional gene expression, to Vgat\u2010positive inhibitory interneurons increased RGC survival compared with Vgat\u2010EGFP controls and Vglut2\u2010lineage Lin28 expression. Vgat\u2010targeted Lin28 also reduced c\u2010fos expression and oscillatory potential\u2010associated differential electroretinogram abnormalities, indicating suppression of ocular hypertension\u2010associated inner retinal hyperactivity. In addition, ocular hypertension was associated with altered sleep architecture, and Vgat\u2010targeted Lin28 expression was associated with mitigation of these alterations. These findings position presynaptic inhibitory retinal circuitry as an early and modifiable contributor to glaucomatous RGC vulnerability.<\/jats:p>","DOI":"10.1002\/advs.78179","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:33:38Z","timestamp":1791351218000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Presynaptic Inhibitory Retinal Circuits for Retinal Ganglion Cell Neuroprotection in Glaucoma"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3294-1780","authenticated-orcid":false,"given":"Eunji","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6481-2730","authenticated-orcid":false,"given":"Chen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2000-1267","authenticated-orcid":false,"given":"Wenjie","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4068-2105","authenticated-orcid":false,"given":"Ian","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1758-2294","authenticated-orcid":false,"given":"Mengwen","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1621-0459","authenticated-orcid":false,"given":"Zuer","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1555-487X","authenticated-orcid":false,"given":"Siyuan","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Binghamton University State University of New York  Binghamton New York USA"},{"name":"Integrative Neuroscience Program Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9840-6732","authenticated-orcid":false,"given":"Qianbin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"issue":"15","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1056\/NEJM199304153281507","article-title":"Open\u2010Angle Glaucoma","volume":"328","author":"Quigley H. 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D.","year":"2021","journal-title":"JAMA"},{"issue":"1","key":"e_1_2_10_4_1","article-title":"Current Medical Therapy And Future Trends In The Management of Glaucoma Treatment","volume":"2020","author":"Cvenkel B.","year":"2020","journal-title":"Journal of Ophthalmology"},{"issue":"1","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1089\/jop.2017.0041","article-title":"Targets of Neuroprotection in Glaucoma","volume":"34","author":"He S.","year":"2018","journal-title":"Journal of Ocular Pharmacology and Therapeutics"},{"issue":"16","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1016\/j.neuron.2022.06.003","article-title":"Core Transcription Programs Controlling Injury\u2010Induced Neurodegeneration of Retinal Ganglion Cells","volume":"110","author":"Tian F.","year":"2022","journal-title":"Neuron"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"S284","DOI":"10.1016\/S0039-6257(01)00200-4","article-title":"Efficacy and Safety of Memantine, an NMDA\u2010Type Open\u2010Channel Blocker, for Reduction of Retinal Injury Associated With Experimental Glaucoma in Rat and Monkey","volume":"45","author":"Hare W.","year":"2001","journal-title":"Survey of Ophthalmology"},{"issue":"10","key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"4515","DOI":"10.1167\/iovs.08-2078","article-title":"\u03b12 Adrenergic Modulation of NMDA Receptor Function as a Major Mechanism of RGC Protection in Experimental Glaucoma and Retinal Excitotoxicity","volume":"49","author":"Dong C.\u2010J.","year":"2008","journal-title":"Investigative Opthalmology & Visual Science"},{"issue":"1","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1023\/A:1014854606309","article-title":"Glutamate\u2010Induced Excitotoxicity in Retina: Neuroprotection with Receptor Antagonist, Dextromethorphan, but Not With Calcium Channel Blockers","volume":"27","author":"Calzada J. I.","year":"2002","journal-title":"Neurochemical research"},{"issue":"11","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.3390\/antiox9111031","article-title":"Glaucoma and Antioxidants: Review and Update","volume":"9","author":"Garcia\u2010Medina J. J.","year":"2020","journal-title":"Antioxidants"},{"issue":"11","key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.3390\/biology10111181","article-title":"Cell\u2010Based Neuroprotection of Retinal Ganglion Cells in Animal Models of Optic Neuropathies","volume":"10","author":"Hu Y.","year":"2021","journal-title":"Biology"},{"issue":"5903","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1126\/science.1161566","article-title":"Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN\/mTOR Pathway","volume":"322","author":"Park K. 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