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Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization.
Authors:V Lambert  C Munaut  A No?l  F Frankenne  K Bajou  R Gerard  P Carmeliet  M P Defresne  J M Foidart  J M Rakic
Affiliation:Laboratory of Tumor and Development Biology, University of Liège, B-4000 Liège, Belgium. vincent.lambert@ulg.ac.be
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.
Keywords:
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