Correlation of vascular permeability factor/vascular endothelial growth factor with extraretinal neovascularization in the rat

Objective: To determine whether neovascularization was spatially correlated with the distribution of messenger RNA for vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). Methods: Neonatal rats were raised 8 days in 80% oxygen with daily intervals of relative hypoxia in room air, then transferred to room air for 5, 7, or 10 additional days. In situ hybridization for VPF/VEGF expression and avascular area were examined in retinas from oxygen-exposed animals and room-air controls. Severity of neovascularization was scored. Results: The inner nuclear layer of oxygen-exposed retinas exhibited a continuous intense band of VPF/VEGF messenger RNA expression across the peripheral avascular zone that dropped sharply in vascular retina. Neovascularization occurred adjacent to regions of greatest expression. Controls had much lower expression and smaller avascular regions. The VPF/VEGF 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 layer. Conclusion: The expression of VPF/VEGF message was spatially and quantitatively correlated with the neovascularization.