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Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization
Author(s) -
Lambert Vincent,
Munaut Carine,
Noël Agnès,
Frankenne Francis,
Bajou Khalid,
Gerard Robert,
Carmeliet Peter,
Paule Defresne Marie,
Foidart Jean-Michel,
Rakic Jean-Marie
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fsb2fj000393com
Subject(s) - choroidal neovascularization , plasminogen activator , plasminogen activator inhibitor 1 , angiogenesis , neovascularization , macular degeneration , tissue plasminogen activator , medicine , diabetic retinopathy , cancer research , t plasminogen activator , ophthalmology , endocrinology , diabetes mellitus
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).