Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization

V Lambert, C Munaut, F Frankenne, K Bajou… - FASEB …, 2001 - orbi.uliege.be
V Lambert, C Munaut, F Frankenne, K Bajou, R Gerard, P Carmeliet, MP Defresne…
FASEB Journal, 2001orbi.uliege.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 …
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.
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