Age-related macular degeneration (AMD) is the primary cause of blindness in Western developed countries. The disease takes two distinct forms: a slow-progressing form referred to as ‘dry' or ‘avascular' AMD, for which there are no treatment options, and a rapidly progressing form referred to as ‘wet' or ‘neovascular' AMD. Neovascular AMD, which is responsible for most cases of legal blindness, appears to be the result of an imbalance of antiangiogenic and proangiogenic activities in the choroid-Bruch's membrane–retina complex. Intravitreal injection of antiangiogenic factors, specifically inhibitors of VEGF, results in significant vision recovery in 30–40% of patients, suggesting that the retinal pigment epithelium and photoreceptors are not irreversibly damaged in these patients. Since inhibition of neovascularization in these patients requires frequent intravitreal injections of anti-VEGFs, a number of investigators have suggested that transplantation of genetically modified cells secreting antiangiogenic and neurogenic factors may be a more permanent and more functional treatment. Most investigators have used virally mediated transfection to genetically modify retinal pigment epithelial cells since nonvirally mediated gene transfer protocols are not efficient. However, novel microelectroporation-mediated gene transfer protocols have been devised that can transfect pigment cells stably and with very high efficiency. Using these protocols, retinal pigment epithelial and iris pigment epithelial cells have been transfected with pigment epithelium-derived factor (PEDF), an antiangiogenic and neurogenic factor, and have been shown to overexpress PEDF after many passages in culture. Subretinal transplantation of pigment cells transfected with PEDF and possibly other factors, should lead to a more permanent treatment of neovascular AMD.