{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T17:29:58Z","timestamp":1786728598082,"version":"build-2736575974"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2]]},"abstract":"\n Purpose:<\/jats:title>\n This study was designed to investigate the primary targets and possible mechanisms of ranitidine (Ra) against diabetic retinopathy (DR).<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Single-cell sequencing technology and the SPIED3 platform were employed to characterize key genes in retinal M\u00fcller cells (RMCs) of diabetic mice and identify potential small-molecule compounds separately. The effects of small-molecule compounds on the cell viability and proliferative capacity of mouse retinal M\u00fcller cells (rMC-1) cultured in high-glucose (HG) were evaluated using the cell counting kit-8 (cck-8) and 5-ethyl-2-deoxyuridine (Edu) assay. Glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), and Fe\n 2+<\/jats:sup>\n were identified as indicators of ferroptosis. Then, network pharmacology was used to predict specific targets for Ra. Western blotting was used to identify ferroptosis-related proteins, including glutathione peroxidase 4 (GPX4), cystine\/glutamate transporter (xCT), serine\/threonine-protein kinase\n AKT1<\/jats:italic>\n , and glycogen synthase kinase-3\n \u03b2<\/jats:italic>\n (\n GSK3\u03b2<\/jats:italic>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n The predicted results suggested that the potential mechanism of RMCs damage in diabetic mice is associated with ferroptosis. The cck-8 results indicated Ra played a regulatory role in HG-induced rMC-1 by enhancing cell viability. Besides, Edu results showed that Ra promoted the proliferation of rMC-1 cells. Network pharmacological analyses predicted a potential mechanism of Ra effect in HG-induced rMC-1, mainly associated with the\n AKT1<\/jats:italic>\n and\n GSK3\u03b2<\/jats:italic>\n genes. Phenotypically, Ra elevated intracellular GSH levels, while reducing MDA, Fe\u00b2\u207a, and ROS concentrations. Mechanistically, Ra increased xCT and GPX4 expression through the promotion of\n AKT1<\/jats:italic>\n \/\n GSK3\u03b2<\/jats:italic>\n phosphorylation, thereby alleviating ferroptosis in HG-induced rMC-1 cells.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n The study highlighted that the mechanism of DR is closely associated with ferroptosis and demonstrated that Ra inhibits HG-induced ferroptosis of rMC-1 cells by regulating the\n AKT1<\/jats:italic>\n \/\n GSK3\u03b2<\/jats:italic>\n signaling pathway, thereby providing a theoretical basis for using Ra in managing DR.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/ijo.ijo_1522_25","type":"journal-article","created":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T13:00:20Z","timestamp":1769346020000},"page":"250-258","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Ranitidine protects M\u00fcller cells against ferroptosis in diabetic retinopathy by regulating the AKT1\/GSK3\u03b2 pathway"],"prefix":"10.4103","volume":"74","author":[{"given":"Wei","family":"He","sequence":"first","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China"},{"name":"Department of Ophthalmology, The First People\u2019s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, P.R. China"},{"name":"Medical School, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialong","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Yunnan Digestive Endoscopy Clinical Medical Center, The First People\u2019s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongjian","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Basic and Clinical Medicine, The First People\u2019s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Mei","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China"},{"name":"Department of Ophthalmology, The First People\u2019s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, P.R. China"},{"name":"Medical School, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,1,24]]},"reference":[{"key":"R1-20260420","first-page":"387","article-title":"Prevalence of diabetic retinopathy in Type 2 diabetes in developing and developed countries","volume":"30","author":"Ruta","year":"2013","journal-title":"Diabet Med"},{"key":"R2-20260420","first-page":"260","article-title":"Diabetic retinopathy: Global prevalence, major risk factors, screening practices and public health challenges: A review","volume":"44","author":"Ting","year":"2016","journal-title":"Clin Exp Ophthalmol"},{"key":"R3-20260420","first-page":"556","article-title":"Global prevalence and major risk factors of diabetic retinopathy","volume":"35","author":"Yau","year":"2012","journal-title":"Diabetes Care"},{"key":"R4-20260420","first-page":"843","article-title":"Diabetic retinopathy\u2013An underdiagnosed and undertreated inflammatory, neuro-vascular complication of 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