| First Author | Rosales MAB | Year | 2019 |
| Journal | Life Sci Alliance | Volume | 2 |
| Issue | 3 | PubMed ID | 31101737 |
| Mgi Jnum | J:280338 | Mgi Id | MGI:6368421 |
| Doi | 10.26508/lsa.201800212 | Citation | Rosales MAB, et al. (2019) Loss of PGC-1alpha in RPE induces mesenchymal transition and promotes retinal degeneration. Life Sci Alliance 2(3) |
| abstractText | The retinal pigment epithelium (RPE) supports visual processing and photoreceptor homeostasis via energetically demanding cellular functions. Here, we describe the consequences of repressing peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha), a master regulator of mitochondrial function and biogenesis, on RPE epithelial integrity. The sustained silencing of PGC-1alpha in differentiating human RPE cells affected mitochondria/autophagy function, redox state, and impaired energy sensor activity ultimately inducing epithelial to mesenchymal transition (EMT). Adult conditional knockout of PGC-1 coactivators in mice resulted in rapid RPE dysfunction and transdifferentiation associated with severe photoreceptor degeneration. RPE anomalies were characteristic of autophagic defect and mesenchymal transition comparable with the ones observed in age-related macular degeneration. These findings demonstrate that PGC-1alpha is required to maintain the functional and phenotypic status of RPE by supporting the cells' oxidative metabolism and autophagy-mediated repression of EMT. |
