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The dysfunction of retinal pigment epithelial (RPE) cells is a central event in AMD, a process that shares key hallmarks with broader cellular aging, particularly the progressive decline in mitochondrial function. In this study, we investigated how a common environmental stressor\u2014blue light\u2014triggers a key pathological transformation, epithelial\u2010mesenchymal transition (EMT), in RPE cells by specifically disrupting mitochondrial dynamics, a core pillar of cellular aging. Using an in\u00a0vitro model of human RPE cells, we demonstrated that blue light exposure induces a marked shift in mitochondrial dynamics towards excessive fission. This imbalance directly resulted in mitochondrial dysfunction, elevated oxidative stress, and served as the critical driver for the initiation of EMT. Importantly, pharmacological inhibition of the mitochondrial fission GTPase Dynamin\u2010related protein 1 (Drp1) with Mdivi\u20101 effectively restored mitochondrial network homeostasis, rescued mitochondrial function, and fully reversed the EMT phenotype. These findings were corroborated in a mouse model of blue light\u2010induced retinal damage, where Drp1 inhibition successfully preserved retinal light responses, mitigated structural degeneration, and slowed disease progression. Our study demonstrates that Drp1\u2010mediated excessive mitochondrial fission drives EMT in RPE cells under blue light, linking this mechanism to AMD progression. Consequently, targeting mitochondrial dynamics to maintain cellular homeostasis emerges as a promising and broadly applicable geroscience\u2010based strategy for mitigating age\u2010related tissue dysfunction.<\/jats:p>","DOI":"10.1111\/acel.70416","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T07:37:29Z","timestamp":1771313849000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dynamin\u2010Related Protein 1\u2010Dependent Disruption of Mitochondrial Homeostasis Drives Blue Light\u2010Induced Epithelial\u2010Mesenchymal Transition in Retinal Aging"],"prefix":"10.1111","volume":"25","author":[{"given":"Zhi\u2010Yuan","family":"Li","sequence":"first","affiliation":[{"name":"Guangdong\u2010Hongkong\u2010Macau Institute of CNS Regeneration, Key Laboratory of CNS Regeneration (Jinan University)\u2010Ministry of Education, Guangdong Key Laboratory of Non\u2010Human Primate Research Jinan University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dashuang","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hongkong\u2010Macau Institute of CNS Regeneration, Key Laboratory of CNS Regeneration (Jinan University)\u2010Ministry of Education, Guangdong Key Laboratory of Non\u2010Human Primate Research Jinan University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxia","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hongkong\u2010Macau Institute of CNS Regeneration, Key Laboratory of CNS Regeneration (Jinan University)\u2010Ministry of Education, Guangdong Key Laboratory of Non\u2010Human Primate Research Jinan University  Guangzhou P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hongkong\u2010Macau Institute of CNS Regeneration, Key Laboratory of CNS Regeneration (Jinan University)\u2010Ministry of Education, Guangdong Key Laboratory of Non\u2010Human Primate Research Jinan University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-019-02409-6"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04595-6"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1256932"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101735"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11030450"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107380"},{"issue":"3","key":"e_1_2_14_8_1","first-page":"1535","article-title":"Recent Advances in Our Understanding of Age\u2010Related Macular Degeneration: Mitochondrial Dysfunction, Redox Signaling, and the Complement System","volume":"16","author":"Buonfiglio F.","year":"2024","journal-title":"Aging and Disease"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096365"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07367-9"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70018"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.08.003"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06199-7"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-71119-6"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00265-2"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.109207"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107537"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-24132"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.626117"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12020207"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2015.09.002"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2024.10.301"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2024.109823"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.07.158"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3003453"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-023-01948-8"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.180"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0086"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010025\u201008352\u2010y"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00432"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03068-w"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106250"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.303537"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.125.052689"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2025.08.007"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1039\/c5pp00188a"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109866"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2022.07.003"},{"issue":"3","key":"e_1_2_14_40_1","first-page":"3563","article-title":"Cigarette Smoke\u2010Induced EGFR Activation Promotes Epithelial Mesenchymal Migration of Human Retinal Pigment Epithelial Cells Through Regulation of the FAK\u2010Mediated Syk\/Src Pathway","volume":"17","author":"Park G. 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