Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization

Abstract

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.—Lambert, V., Munaut, C., Noel, A., Frankenne, F., Bajou, K., Gerard, R., Carmeliet, P., Defresne, M. P., Foidart, J.‐M., Rakic, J.‐M. Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization. FASEB J. 15, 1021–1027 (2001).