Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization

High levels of the plasminogen activators, but also their inhibitor, plasmi nog en activator inhibitor 1 (PAI-1), have been documented in neovasculariz ation of severe ocular pathologies such as diabetic retinopathy or age-rela ted macular degeneration (AMD). AMD is the primary cause of irreversible ph otoreceptors loss, and current therapies are limited. PAI-1 has recently be en shown to be essential for tumoral angiogenesis. We report here that defi cient PAI-1 expression in mice prevented the development of subretinal chor oidal angiogenesis induced by laser photocoagulation. When systemic and loc al PAI-1 expression was achieved by intravenous injection of a replication- defective adenoviral vector expressing human PAI-1 cDNA, the wild-type patt ern 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 oc ular anti-angiogenic strategies.