Vascular endothelial growth factor is sufficient to produce iris neovascularization and neovascular glaucoma in a nonhuman primate

Objective: To determine whether the angiogenic peptide vascular endothelial growth factor (VEGF) is sufficient to produce iris neovascularization in a nonhuman primate (Macaca fascicularis). Methods: Eight eyes of 4 animals were studied. The 165-amino acid isoform of human recombinant VEGF (VEGF(165)) was injected into the vitreous of 5 cynomolgus monkey eyes (doses ranging from 0.25-2.5 mu g per injection). Equal amounts of inactivated human recombinant VEGF (2 eyes) or vehicle (1 eye) were injected into contralateral control eyes. Eyes were assessed by slit-lamp biomicroscopy, tonometry, iris color photography, fluorescein angiography, histopathologic examination, and immunostaining with antibodies against proliferating cell nuclear antigen. Results: All 5 bioactive VEGF-injected eyes developed neovascularization with dilated and tortuous iris vessels that leaked fluorescein. None of the 3 control eyes exhibited any iris vascular changes. Inflammation was absent in both treatment groups. A dose response to VEGF was observed in the single animal that received 2.5 mu g and 0.25 mu g in the right and left eyes, respectively. Iris vessel endothelial cells were positive for proliferating cell nuclear antigen in the bioactive VEGF-injected eyes only. Injections of 1.25 mu g of VEGF every 3 days during a 30-day period produced advanced iris neovascularization, ectropion uvea, and neovascular glaucoma. Conclusions: Intravitreal injections of recombinant human VEGF(165) in amounts comparable with those measured in eyes with active neovascularization are sufficient to produce noninflammatory iris neovascularization in a nonhuman primate. Prolonged exposure to VEGF(165) can produce ectropion uveae and neovascular glaucoma.