Gene Therapy for Neovascular Retinopathies

Normal control of retinal angiogenesis, the formation of new blood vessels in either the retinal or choroidal beds from preexisting vasculature, is essential for vision. Conversely, pathological neovascularization (NV) of retinal and choroidal vessels is a key process leading to vision loss in several prevalent ocular diseases, including retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and age-related macular degeneration (AMD). PDR and AMD are the leading causes of blindness in developed countries, and ROP is the leading cause of infant blindness. Proper regulation of retinal vascularization is thought to depend on an equilibrium between ocular vascular growth factors, primarily vascular endothelial growth factor (VEGF) (1), and natural inhibitors of angiogenesis, primarily pigment epithelium-derived factor (PEDF) (2). When this balance becomes disturbed—as may happen, for example, during and after the hyperoxic treatment of premature infants—pathological angiogenesis often occurs that ultimately leads to vision loss.