Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization.
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
V
Laboratory of Tumor and Development Biology, University of Liège, B-4000 Liège, Belgium. vincent.lambert@ulg.ac.be
Munaut
C
C
Noël
A
A
Frankenne
F
F
Bajou
K
K
Gerard
R
R
Carmeliet
P
P
Defresne
M P
MP
Foidart
J M
JM
Rakic
J M
JM
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D020256:Choroidal Neovascularization / Q000503:physiopathology*; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D018076:DNA, Complementary; D017395:Plasminogen Activator Inhibitor 1