PGC-1? regulates normal and pathological angiogenesis in the retina.

ABSTRACT: 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-1? is a transcriptional coactivator that plays a central role in the regulation of cellular metabolism. In skeletal muscle, PGC-1? induces VEGFA expression and powerfully promotes angiogenesis, suggesting a similar role in other tissues. This study investigates the role of PGC-1? during normal and pathological vascularization in the retina. We show that PGC-1? induces the expression of VEGFA in numerous retinal cells, and that PGC-1? expression is strongly induced during postnatal retinal development, coincident with VEGFA expression and angiogenesis. PGC-1?(-/-) 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-1? expression is dramatically induced in the inner nuclear layer of the retina, suggesting that PGC-1? drives pathological neovascularization. In support of this, PGC-1?(-/-) mice subjected to oxygen-induced retinopathy had decreased expression of VEGFA and were protected against pathological neovascularization. These results demonstrate that PGC-1? regulates VEGFA in the retina and is required for normal vessel development and for pathological neovascularization. The data highlight PGC-1? as a novel target in the treatment of neovascular diseases of the eye.

SUBMITTER: Saint-Geniez M 

PROVIDER: S-EPMC3538026 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature