PGC-1α regulates normal and pathological angiogenesis in the retina

Am J Pathol. 2013 Jan;182(1):255-65. doi: 10.1016/j.ajpath.2012.09.003. Epub 2012 Nov 7.


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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gene Expression Regulation / physiology
  • Humans
  • Infant, Newborn
  • Mice
  • Mice, Knockout
  • Neovascularization, Physiologic / physiology*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Retina / growth & development
  • Retina / metabolism
  • Retina / pathology
  • Retinal Neovascularization / metabolism*
  • Retinal Neovascularization / pathology
  • Retinal Neovascularization / prevention & control
  • Retinal Vessels / growth & development
  • Retinal Vessels / metabolism*
  • Retinal Vessels / pathology
  • Retinopathy of Prematurity / metabolism
  • Retinopathy of Prematurity / prevention & control
  • Trans-Activators / biosynthesis
  • Trans-Activators / deficiency
  • Trans-Activators / physiology*
  • Transcription Factors
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics


  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse