{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:58:20Z","timestamp":1792511900402,"version":"4.5.0"},"reference-count":72,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY30141"],"award-info":[{"award-number":["R01EY30141"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000888","name":"W. M. Keck Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101150"],"award-info":[{"award-number":["82101150"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101124"],"award-info":[{"award-number":["82101124"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Subretinal fibrosis significantly contributes to vision loss in neovascular age\u2010related macular degeneration (nAMD). Epithelial\u2010to\u2010mesenchymal transition (EMT) in RPE cells is a key early step in subretinal fibrosis. While mitochondrial dysfunction in RPE is involved, the metabolic and molecular connections between EMT and mitochondria are not well understood. This study explores the role of oxoglutarate carrier (OGC; Slc25a11) on EMT and investigates the molecular mechanisms, focusing on its role in mitochondrial metabolism and GSH transport. OGC\u2010silenced or overexpressed ARPE\u201019 cells were treated with TGF\u2010\u03b22 (10\u2009ng\/mL) for 48\u2009h. EMT markers, cell migration, mtGSH, and mitochondrial bioenergetics and signaling pathways were assessed. In\u00a0vivo, subretinal fibrosis was induced in wild\u2010type and OGC\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice via laser photocoagulation. Fibrosis volume was measured using optical coherence tomography and immunostaining in RPE\u2010choroid flat mounts. OGC silencing aggravated EMT, while overexpression attenuated TGF\u2010\u03b22\u2010induced EMT, cell proliferation, and migration. OGC knockdown significantly enhanced RPE EMT, as evidenced by upregulated expression of \u03b1\u2010SMA, fibronectin, collagen type I, and Slug, while E\u2010cadherin was downregulated. OGC overexpression improved mitochondrial bioenergetics, whereas its inhibition reduced mitochondrial respiration, which was further aggravated by co\u2010treatment with TGF\u2010\u03b22. Loss of OGC promoted cell proliferation and migration through Slug\u2010mediated EMT. OGC depletion stimulated EMT via pSmad2\/3 upregulation, dependent on the PI3K\/AKT signaling pathway activation. In\u00a0vivo studies further demonstrate that subretinal fibrosis was significantly augmented in OGC\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice via TGF\u2010\u03b22\u2010dependent PI3K signaling. In conclusion, modulating OGC expression in RPE affects EMT and mitochondrial function, making OGC a potential therapeutic target for subretinal fibrosis in nAMD.\n                  <\/jats:p>","DOI":"10.1111\/acel.70271","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T15:14:26Z","timestamp":1761664466000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Deficiency of 2\u2010Oxoglutarate Carrier (Slc25a11) Drives\n                    <scp>RPE<\/scp>\n                    Epithelial\u2010to\u2010Mesenchymal Transition and Exacerbates Subretinal Fibrosis in Neovascular Age\u2010Related Macular Degeneration"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3518-7368","authenticated-orcid":false,"given":"Mo","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai Eye Diseases Prevention &amp;Treatment Center\/Shanghai Eye Hospital, School of Medicine Tongji University  Shanghai China"},{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2799-3554","authenticated-orcid":false,"given":"Feng\u2010Juan","family":"Gao","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyi","family":"Tang","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3086-8663","authenticated-orcid":false,"given":"Boya","family":"Lei","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ma","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas R.","family":"Sadda","sequence":"additional","affiliation":[{"name":"Jules Stein Eye Institute, David Geffen School of Medicine University of California at Los Angeles  Los Angeles California USA"},{"name":"Department of Ophthalmology, David Geffen School of Medicine University of California\u2010Los Angeles  Los Angeles California USA"},{"name":"Doheny Eye Institute  Pasadena California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Kannan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, David Geffen School of Medicine University of California\u2010Los Angeles  Los Angeles California USA"},{"name":"Doheny Eye Institute  Pasadena California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parameswaran G.","family":"Sreekumar","sequence":"additional","affiliation":[{"name":"Doheny Eye Institute  Pasadena California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8441-9690","authenticated-orcid":false,"given":"Gezhi","family":"Xu","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3810"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.06.018"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.08.022"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.02.00262402"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101201"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-2463"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.11.016"},{"key":"e_1_2_10_9_1","first-page":"517","article-title":"Interleukin\u20106 Promotes Proliferative Vitreoretinopathy by Inducing Epithelial\u2010Mesenchymal Transition via the JAK1\/STAT3 Signaling Pathway","volume":"26","author":"Chen X.","year":"2020","journal-title":"Molecular Vision"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)37484-1"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01545-4"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2013.10.019"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054509"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13091-8"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.12.004"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017827"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.302"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121753"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11152336"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12020207"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fopht.2022.1060087"},{"key":"e_1_2_10_22_1","first-page":"1222","article-title":"Transcriptional Factors Associated With Epithelial\u2010Mesenchymal Transition in Choroidal Neovascularization","volume":"17","author":"Hirasawa M.","year":"2011","journal-title":"Molecular Vision"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.101921"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155117"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.11.030"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.03.009"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.11.014"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102021"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/dgd.12630"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2020.100858"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)84087-5"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2618-6"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103406"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2006.03.001"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.01.036"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-02033-7"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.11.029"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106250"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.09.026"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adf4154"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02546-3"},{"key":"e_1_2_10_42_1","first-page":"855","article-title":"Transdifferentiated Retinal Pigment Epithelial Cells Are Immunoreactive for Vascular Endothelial Growth Factor in Surgically Excised Age\u2010Related Macular Degeneration\u2010Related Choroidal Neovascular Membranes","volume":"37","author":"Lopez P. F.","year":"1996","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-06773-7"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.13.47"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.10.018"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.07.018"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11081175"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.092593"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24165"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.109046"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2011.10.021"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00151"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124271"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094701"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.08.001"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10050661"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.66.6.30"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9050411"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2117396119"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.65.12.26"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11102080"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-25686"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15060771"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04025-w"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.405738"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(13)70145-1"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abn2879"},{"key":"e_1_2_10_68_1","first-page":"1120","article-title":"GSK3beta Inhibits Epithelial\u2010Mesenchymal Transition via the Wnt\/Beta\u2010Catenin and PI3K\/Akt Pathways","volume":"11","author":"Zhang C.","year":"2018","journal-title":"International Journal of Ophthalmology"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR-D-23-01642"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019456"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-022-00778-0"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2008.03.008"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00501"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70271","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70271","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70271","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:28:44Z","timestamp":1780457324000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":72,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/acel.70271"],"URL":"https:\/\/doi.org\/10.1111\/acel.70271","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,28]]},"assertion":[{"value":"2025-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70271"}}