Natural history of choroidal neovascularization induced by vascular endothelial growth factor in the primate

Background: A new model of choroidal neovascularization (CNV) has been deve loped in the primate by implanting vascular endothelial growth factor (VEGF )-impregnated microspheres in the subretinal space. Methods: CNV was induce d in Macaca mulatta monkeys by implanting VEGF-implegnated gelatin microsph eres in the subretinal space. Progression of CNV was followed for 24 weeks after surgery using fluorescein angiography. Eyes were enucleated at variou s time points, and lesions were evaluated for evidence of CNV by light micr oscopy and by immunohistochemical staining. Results. CNV developed in 12 (9 2%) of 13 eyes. Fluorescein leakage was first observed in the 2nd postopera tive week and was apparent for the following 12 weeks. CD31 staining for en dothelial cells was first observed at day 7 and was evident for the followi ng 8 weeks. Glial fibrillary acidic protein staining revealed a glial adhes ion between the proliferative membrane and the retina at 6 weeks after impl antation. Smooth muscle actin-positive cells were found a +2 weeks and rema ined prominent for at least the next 6 weeks. Cytokeratin-positive retinal pigment epithelial (RPE) cells, first identified in the proliferative membr ane at day 3, predominated throughout the growth of the membrane. Macrophag es (RAM-II Positive) were present at day 3 but were no longer observed afte r day 7. Conclusion: In monkeys, subretinal implantation of VEGF-impregnate d gelatin microspheres leads to the development of CNV. Early, disciform an d reparative stages of CNV were observed, similar to those seen in humans. This model will be useful for studying the pathogenesis of CNV and for eval uating potential treatment strategies.