{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T18:45:27Z","timestamp":1769366727105,"version":"3.49.0"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81770945"],"award-info":[{"award-number":["81770945"]}]},{"name":"National Natural Science Foundation of China","award":["81970809"],"award-info":[{"award-number":["81970809"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Retinal neurodegeneration is a major cause of vision loss. Retinoic acid signaling is critical for the maintenance of retinal function, and its dysfunction can cause retinal neurodegeneration. However, the therapeutic effects of retinoic acid drugs on retinal neurodegeneration remain unclear. In this study, we designed a novel retinoic acid drug called EYE-503 and investigated its therapeutic effects of EYE-503 on retinal neurodegeneration. The optic nerve crush (ONC) model was selected for the retinal neurodegeneration study. H&amp;E staining, TUNEL staining, immunofluorescence staining, and visual electrophysiology assays were performed to determine the role of EYE-503 in retinal neurodegeneration in vivo. The CCK-8 assay, EdU incorporation assay, PI staining, and flow cytometry assays were performed to investigate the effects of EYE-503 administration on retinal neurodegeneration in vitro. The potential mechanism of EYE-503 in retinal neurodegeneration was investigated by network pharmacology and Western blots. The results showed that EYE-503 administration had no detectable cytotoxicity and tissue toxicity. EYE-503 administration alleviated ONC-induced retinal injury and optic nerve injury in vivo. EYE-503 administration attenuated retinal ganglion cell apoptosis, inhibited reactive gliosis, and retarded the progression of retinal neurodegeneration. Mechanistically, EYE-503 regulated retinal neurodegeneration by targeting the JNK\/p38 signaling pathway. This study suggests that EYE-503 is a promising therapeutic agent for retinal neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/ph16071033","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T01:52:35Z","timestamp":1689904355000},"page":"1033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["EYE-503: A Novel Retinoic Acid Drug for Treating Retinal Neurodegeneration"],"prefix":"10.3390","volume":"16","author":[{"given":"Sha","family":"Liu","sequence":"first","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210093, China"},{"name":"The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuke","family":"Ji","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210093, China"},{"name":"The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210093, China"},{"name":"The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Ren","sequence":"additional","affiliation":[{"name":"Eye Institute and Department of Ophthalmology, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junya","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210093, China"},{"name":"The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianjing","family":"Yang","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210093, China"},{"name":"The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiumiao","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210093, China"},{"name":"The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Yao","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210093, China"},{"name":"The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1722-023X","authenticated-orcid":false,"given":"Xin","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biao","family":"Yan","sequence":"additional","affiliation":[{"name":"Eye Institute and Department of Ophthalmology, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200433, China"},{"name":"NHC Key Laboratory of Myopia, Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai 200031, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.jns.2016.12.044","article-title":"Ischemic optic neuropathy as a model of neurodegenerative disorder: A review of pathogenic mechanism of axonal degeneration and the role of neuroprotection","volume":"375","author":"Khalilpour","year":"2017","journal-title":"J. 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