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* Laboratory of Tumor and Development Biology, University of Liège, B-4000 Liège, Belgium;
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Campus Gasthuisberg, University of Leuven, Belgium;
Laboratory of Cytology and Histolgy, University of Liège, B-4000 Liège, Belgium; and
Department of Ophthalmology, University Hospital, Sart-Tilman, B-4000 Liège, Belgium
1Correspondence: Laboratory of Tumor and Development Biology, University of Liège, Pathology Tower (B23), Sart-Tilman, B-4000 Liège, Belgium. E-mail: vincent.lambert{at}ulg.ac.be
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., Noël, 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.
Key Words: angiogenesis • retinal disease • proteases • viral vector • macular degeneration
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