VASCULAR ENDOTHELIAL GROWTH-FACTOR VASCULAR-PERMEABILITY FACTOR EXPRESSION IN A MOUSE MODEL OF RETINAL NEOVASCULARIZATION

Neovascular diseases of the retina are a major cause of blindness worl dwide. Hypoxia is thought to be a common precursor to neovascularizati on in many retinal diseases, but the factors involved in the hypoxic n eovascular response have not been fully identified. To investigate the role of vascular endothelial growth factor/vascular permeability fact or (VEGF/VPF) in retinal neovascularization, the expression of VEGF/VP F mRNA and protein were studied in a mouse model of proliferative reti nopathy. RNA (Northern) blot analysis revealed that retinal VEGF/VPF m RNA expression increased 3-fold between 6 and 12 hr of relative retina l hypoxia and remained elevated during the development of neovasculari zation. In situ hybridization localized VEGF/VPF mRNA to cells bodies in the inner nuclear layer of the retina. Immunohistochemical confocal microscopy demonstrated that VEGF/VPF protein levels increase with a time course similar to that of the mRNA. The cells in the inner nuclea r layer of the retina that produce VEGF/VPF were identified morphologi cally as Muller cells. These data suggest that VEGF/WF expression in t he retina plays a central role in the development of retinal ischemia- induced ocular neovascularization.