Other
10 Authors
- Wu W,
- Ma JX,
- Cai J,
- Panzarin C,
- Hara M,
- Takahashi Y,
- Ma X,
- Griffin CT,
- Schafer CM,
- Zhou J
| First Author | Ma X | Year | 2024 |
| Journal | Commun Biol | Volume | 7 |
| Issue | 1 | Pages | 1075 |
| PubMed ID | 39223298 | Mgi Jnum | J:353569 |
| Mgi Id | MGI:7715390 | Doi | 10.1038/s42003-024-06773-7 |
| Citation | Ma X, et al. (2024) Deficient RPE mitochondrial energetics leads to subretinal fibrosis in age-related neovascular macular degeneration. Commun Biol 7(1):1075 |
| abstractText | 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, TGFbeta(2) induces fibrosis by activating a Warburg-like effect, i.e. increased glycolysis and decreased mitochondrial respiration through ERK-dependent CPT1A degradation. Moreover, VLDLR blocks the formation of the TGFbeta receptor I/II complex by interacting with unglycosylated TGFbeta receptor II. In conclusion, VLDLR suppresses fibrosis by attenuating TGFbeta(2)-induced metabolic reprogramming, and CPT1A is a potential target for treating subretinal fibrosis. |
