Deficient RPE mitochondrial energetics leads to subretinal fibrosis in age-related neovascular macular degeneration.

ABSTRACT: Subretinal fibrosis permanently impairs the vision of patients with neovascular age-related macular degeneration. Despite emerging evidence revealing the association between disturbed metabolism in retinal pigment epithelium (RPE) and subretinal fibrosis, the underlying mechanism remains unclear. In the present study, single-cell RNA sequencing revealed, prior to subretinal fibrosis, genes in mitochondrial fatty acid oxidation are downregulated in the RPE lacking very low-density lipoprotein receptor (VLDLR), especially the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A). We found that overexpression of CPT1A in the RPE of Vldlr^-/- mice suppresses epithelial-to-mesenchymal transition and fibrosis. Mechanistically, TGFβ₂ induces fibrosis by activating a

SUBMITTER: Ma X 

PROVIDER: S-EPMC11369096 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature