{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T22:48:52Z","timestamp":1788043732290,"version":"build-2784847793"},"reference-count":71,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271080"],"award-info":[{"award-number":["82271080"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Guangdong Province in China","award":["2024A1515012976"],"award-info":[{"award-number":["2024A1515012976"]}]},{"name":"Guangdong Basic Research Center of Excellence for Major Blinding Eye Diseases Prevention and Treatment","award":["2024-PIZC-045"],"award-info":[{"award-number":["2024-PIZC-045"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Retinal ischemia\u2013reperfusion (I\/R) injury results in irreversible vision loss largely through retinal ganglion cell (RGC) death, with ferroptosis being a key mechanism. This study evaluated the therapeutic potential of the ferroptosis inhibitor Liproxstatin-1 (Lip-1) and deciphered its underlying mechanism. Using a mouse retinal I\/R model and primary RGC cultures subjected to oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R), we demonstrated that Lip-1 effectively inhibits ferroptosis. Lip-1 treatment preserved retinal architecture (as assessed by H&amp;E staining and SD-OCT) and partially restored visual function (as measured by electroretinography). Integrated molecular analyses\u2014including immunofluorescence, Western blotting, and RNA sequencing\u2014showed that Lip-1 downregulates early growth response 1 (EGR1), thereby inhibiting p53 and consequently restoring solute carrier family 7 member 11 (xCT) expression. Crucially, lentivirus-mediated EGR1 knockdown attenuated OGD\/R-induced ferroptosis, confirming its pivotal role. Our work defines a coherent EGR1\u2013p53\u2013xCT signaling axis driving ferroptosis in retinal I\/R injury and identifies Lip-1 as a neuroprotective agent targeting this pathway. These findings establish a druggable ferroptotic cascade and provide a mechanistic rationale for targeting EGR1 in the treatment of ischemic retinopathies.<\/jats:p>","DOI":"10.3390\/antiox15030391","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T09:44:41Z","timestamp":1773999881000},"page":"391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Liproxstatin-1 Attenuates Retinal Ischemia\u2013Reperfusion Injury by Suppressing EGR1-Mediated Ferroptosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Wei","family":"Huang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huishan","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoyi","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weng Ian","family":"Tam","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuheng","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengguo","family":"Zuo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2610-6658","authenticated-orcid":false,"given":"Mingkai","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/S0140-6736(10)61423-7","article-title":"Glaucoma","volume":"377","author":"Quigley","year":"2011","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"271","DOI":"10.7326\/0003-4819-158-4-201302190-00008","article-title":"Comparative effectiveness of treatments for open-angle glaucoma: A systematic review for the U.S. Preventive Services Task Force","volume":"158","author":"Boland","year":"2013","journal-title":"Ann. 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