CORRELATION OF VASCULAR-PERMEABILITY FACTOR VASCULAR ENDOTHELIAL GROWTH-FACTOR WITH EXTRARETINAL NEOVASCULARIZATION IN THE RAT/

Objective: To determine whether neovascularization was spatially corre lated with the distribution of messenger RNA for vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). Methods: Neonat al rats were raised 8 days in 80% oxygen with daily intervals of relat ive hypoxia in room air, then transferred to room air for 5, 7, or 10 additional days. In situ hybridization for VPF/VEGF expression and ava scular area were examined in retinas from oxygen-exposed animals and r oom-air controls. Severity of neovascularization was scored. Results: The inner nuclear layer of oxygen-exposed retinas exhibited a continuo us intense band of VPF/VEGF messenger RNA expression across the periph eral avascular zone that dropped sharply in vascular retina. Neovascul arization occurred adjacent to regions of greatest expression. Control s had much lower expression and smaller avascular regions. The VPF/VEG F messenger RNA expression was most intense in Muller cells, scattered astrocytes, and amacrine cells, strong in retinal pigment-epithelium, and moderate in the remaining inner nuclear layer and ganglion cell l ayer. Conclusion: The expression of VPF/VEGF message was spatially and quantitatively correlated with the neovascularization.