INTRAVITREOUS INJECTIONS OF VASCULAR ENDOTHELIAL GROWTH-FACTOR PRODUCE RETINAL ISCHEMIA AND MICROANGIOPATHY IN AN ADULT PRIMATE

Purpose: The purpose of the study is to determine the effect of exogen ous vascular endothelial growth factor (VEGF) on the primate retina an d its vasculature. Methods: Ten eyes of five animals were studied. Phy siologlcally relevant amounts of the 165 amino acid isoform of human r ecombinant VEGF were injected into the vitreous of six healthy cynomol gus monkey eyes. inactivated human recombinant VEGF or vehicle was inj ected into four contralateral control subject eyes. Eyes were assessed by slit-lamp biomicroscopy, tonometry, fundus color photography, fund us fluorescein angiography, light microscopy, and immunostaining with antibodies against proliferating cell nuclear antigen and factor VIII antigen, Results: Ail six bioactive VEGF-injected eyes developed dilat ed, tortuous retinal vessels that leaked fluorescein. Eyes receiving m ultiple injections of VEGF developed progressively dilated and tortuou s vessels, Venous beading, edema, microaneurysms, intraretinal hemorrh ages and capillary closure with ischemia. The severity of the retinopa thy correlated with the number of VEGF injections. None of the four co ntrol eyes exhibited any abnormal retinal vascular changes. The endoth elial cells of retinal blood vessels were proliferating cell nuclear a ntigen positive only in the bioactive VEGF-injected eyes. Conclusion: Vascular endothelial growth factor is sufficient to produce many of th e vascular abnormalities common to diabetic retinopathy and other isch emic retinopathies, such as hemorrhage, edema, venous beading, capilla ry occlusion with ischemia, microaneurysm formation, and intraretinal vascular proliferation.