Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization

FASEB J. 2001 Apr;15(6):1021-7. doi: 10.1096/fj.00-0393com.

Abstract

High levels of the plasminogen activators, but also their inhibitor, plasminogen activator inhibitor 1 (PAI-1), have been documented in neovascularization of severe ocular pathologies such as diabetic retinopathy or age-related macular degeneration (AMD). AMD is the primary cause of irreversible photoreceptors loss, and current therapies are limited. PAI-1 has recently been shown to be essential for tumoral angiogenesis. We report here that deficient PAI-1 expression in mice prevented the development of subretinal choroidal angiogenesis induced by laser photocoagulation. When systemic and local PAI-1 expression was achieved by intravenous injection of a replication-defective adenoviral vector expressing human PAI-1 cDNA, the wild-type pattern of choroidal angiogenesis was restored. These observations demonstrate the proangiogenic activity of PAI-1 not only in tumoral models, but also in choroidal experimental neovascularization sharing similarities with human AMD. They identify therefore PAI-1 as a potential target for therapeutic ocular anti-angiogenic strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Choroidal Neovascularization / physiopathology*
  • DNA, Complementary / genetics
  • Female
  • Genetic Vectors
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Activator Inhibitor 1 / physiology*
  • Transfection

Substances

  • DNA, Complementary
  • Plasminogen Activator Inhibitor 1