{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:08:46Z","timestamp":1777957726917,"version":"3.51.4"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"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":["81271025"],"award-info":[{"award-number":["81271025"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Age-related macular degeneration (AMD) involves dysfunction of the retinal pigment epithelium (RPE), where cellular senescence and epithelial-mesenchymal transition (EMT) are key pathological features. The upstream mechanisms linking these processes are not fully understood. This study investigates the potential role of ferroptosis in contributing to senescence-associated EMT in RPE cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We utilized an aging mouse model and two cellular models in ARPE-19 cells, induced by D-galactose (D-gal) and low-dose sodium iodate (SI), respectively. Ferroptosis, EMT, and oxidative stress markers were evaluated via immunofluorescence, flow cytometry, and Western blotting. The specific ferroptosis inhibitor Ferrostatin-1 was used to assess the involvement of ferroptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Aged mouse RPE\/choroid complexes and stressed ARPE-19 cells exhibited features of EMT along with increased ferroptosis hallmarks, including lipid peroxidation and iron accumulation. A downregulation of the xCT\/GPX4 anti-ferroptotic axis was observed. Pretreatment with Fer-1 alleviated ferroptosis by reducing iron levels and lipid peroxidation, and restored xCT\/GPX4 expression. Furthermore, Fer-1 attenuated the EMT phenotype, as evidenced by the restoration of epithelial markers and reduction of mesenchymal markers (Vimentin, \u03b1-SMA) in both D-gal and SI models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that ferroptosis may contribute to linking RPE senescence with EMT, potentially via oxidative stress pathways. The combined targeting of both senescence and ferroptosis could therefore represent a potential therapeutic strategy for addressing RPE dysfunction and AMD progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1718715","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T06:38:11Z","timestamp":1770964691000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The contribution of ferroptosis to the epithelial-mesenchymal transition phenotype in models of age-related macular degeneration"],"prefix":"10.3389","volume":"14","author":[{"given":"Xingyu","family":"Yang","sequence":"first","affiliation":[{"name":"Eye Center, Renmin Hospital of Wuhan University","place":["Wuhan, China"]},{"name":"Eye Institute of Wuhan University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weichen","family":"Xu","sequence":"additional","affiliation":[{"name":"Eye Center, Renmin Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Xie","sequence":"additional","affiliation":[{"name":"Eye Center, Renmin Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Guo","sequence":"additional","affiliation":[{"name":"Eye Center, Renmin Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feiyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Eye Center, Renmin Hospital of Wuhan University","place":["Wuhan, China"]},{"name":"Eye Institute of Wuhan University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiqiao","family":"Xing","sequence":"additional","affiliation":[{"name":"Eye Center, Renmin Hospital of Wuhan University","place":["Wuhan, China"]},{"name":"Eye Institute of Wuhan University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changzheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Eye Center, Renmin Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"109772","DOI":"10.1016\/j.exer.2023.109772","article-title":"Optimizing the sodium iodate model: effects of dose, gender, and age","volume":"239","author":"Anderson","year":"2024","journal-title":"Exp. 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