REQUIREMENT FOR VASCULAR ENDOTHELIAL GROWTH-FACTOR IN WOUND-RELATED AND INFLAMMATION-RELATED CORNEAL NEOVASCULARIZATION

PURPOSE. Vascular endothelial growth factor (VEGF) is required for vas cular development and for ischemia-related tumor, iris, and retinal ne ovascularization. The role of VEGF in inflammatory corneal neovascular ization is unknown and was investigated in these studies. METHODS. A r at model was used in which removal of the corneal and limbal epitheliu m resulted in circumferential neovascularization. Corneal VEGF mRNA le vels were quantified with ribonuclease protection assays, and VEGF pro tein was studied in situ using immunohistochemical analysis. Controlle d-release pellets containing anti-VEGF antibodies were implanted into the corneal stroma and were used to determine the requirement for VEGF in corneal neovascularization. RESULTS. VEGF mRNB and protein were in duced to high levels after corneal injury and were temporally and spat ially correlated with inflammation and neovascularization. VEGF immuno reactivity was localized primarily to the inflammatory cells invading the wounded cornea. The specific inhibition of VEGF bioactivity with n eutralizing antibodies potently suppressed corneal neovascularization. CONCLUSIONS. These data are the first to demonstrate that VEGF may be required for inflammatory neovascularization of the rat cornea and to identify VEGF as a functional endogenous corneal angiogenic factor.