Fibroblast growth factor-2 (
FGF2) is a potent
mitogen for vascular endothelial cells and exogenous administration of
FGF2 stimulates angiogenesis. However, increased expression of
FGF2 in the retina does not cause angiogenesis. One possible explanation is that
FGF2 may not be capable of initiating angiogenesis unless it is administered in pharmacologic levels or there is coexpression of another
angiogenic factor. Alternatively, there may be control mechanisms that sequester
FGF2 in vivo, preventing it from manifesting its in vitro angiogenic activity. We tested the first hypothesis by crossing mice that express
FGF2 in the retina with mice that express
vascular endothelial growth factor (
VEGF) in the retina. Surprisingly, despite comparable levels of
VEGF expression, mice that expressed both
FGF2 and
VEGF had significantly less neovascularization than mice that expressed
VEGF alone. The second hypothesis was tested by treating Rho/
FGF2 transgenic mice with low-intensity
laser photocoagulation that disrupts photoreceptors, but does not
rupture Bruch's membrane, or intense
laser that
ruptures Bruch's membrane. In Rho/
FGF2 transgenics, but not wild type mice,
choroidal neovascularization developed in areas of low-intensity
laser. Both wild type and transgenic mice developed
choroidal neovascularization in areas of intense
laser that ruptured Bruch's membrane, but the area of neovascularization was significantly greater in transgenics. These data suggest that increased
retinal expression of
FGF2 is angiogenic only when it is accompanied by cell injury that overcomes sequestration control mechanisms.