| First Author | Saint-Geniez M | Year | 2013 |
| Journal | Am J Pathol | Volume | 182 |
| Issue | 1 | Pages | 255-65 |
| PubMed ID | 23141926 | Mgi Jnum | J:192235 |
| Mgi Id | MGI:5464205 | Doi | 10.1016/j.ajpath.2012.09.003 |
| Citation | Saint-Geniez M, et al. (2013) PGC-1alpha regulates normal and pathological angiogenesis in the retina. Am J Pathol 182(1):255-65 |
| abstractText | Neovascular diseases of the eye are the most common causes of blindness worldwide. The mechanisms underlying pathological neovascularization in the retina remain incompletely understood. PGC-1alpha is a transcriptional coactivator that plays a central role in the regulation of cellular metabolism. In skeletal muscle, PGC-1alpha induces VEGFA expression and powerfully promotes angiogenesis, suggesting a similar role in other tissues. This study investigates the role of PGC-1alpha during normal and pathological vascularization in the retina. We show that PGC-1alpha induces the expression of VEGFA in numerous retinal cells, and that PGC-1alpha expression is strongly induced during postnatal retinal development, coincident with VEGFA expression and angiogenesis. PGC-1alpha(-/-) mice have a significant reduction of early retinal vascular outgrowth, and reduced density of capillaries and number of main arteries and veins as adults. In the oxygen-induced retinopathy model of retinopathy of prematurity, PGC-1alpha expression is dramatically induced in the inner nuclear layer of the retina, suggesting that PGC-1alpha drives pathological neovascularization. In support of this, PGC-1alpha(-/-) mice subjected to oxygen-induced retinopathy had decreased expression of VEGFA and were protected against pathological neovascularization. These results demonstrate that PGC-1alpha regulates VEGFA in the retina and is required for normal vessel development and for pathological neovascularization. The data highlight PGC-1alpha as a novel target in the treatment of neovascular diseases of the eye. |
