Deficiency of 2-Oxoglutarate Carrier (Slc25a11) Drives RPE Epithelial-to-Mesenchymal Transition and Exacerbates Subretinal Fibrosis in Neovascular Age-Related Macular Degeneration.

ABSTRACT: Subretinal fibrosis significantly contributes to vision loss in neovascular age-related macular degeneration (nAMD). Epithelial-to-mesenchymal 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-silenced or overexpressed ARPE-19 cells were treated with TGF-β2 (10 ng/mL) for 48 h. EMT markers, cell migration, mtGSH, and mitochondrial bioenergetics and signaling pathways were assessed. In vivo, subretinal fibrosis was induced in wild-type

SUBMITTER: Wang M 

PROVIDER: S-EPMC12686559 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature