AAV-mediated gene supply for treatment of degenerative and neovascular retinal diseases

Common blinding diseases that are currently untreatable include conditions characterized by progressive neuronal degeneration, such as retinitis pigmentosa, leber congenital amaurosis or glaucoma, or characterized by ocular neovascularization, like wet age-related macular degeneration, proliferative diabetic retinopathy and retinopathy of prematurity. The pathogenic mechanisms underlying either neuronal degeneration or new vessel formation may be similar and independent of the mutation underlying the disease, thus allowing to test therapeutic strategies acting downstream of the primary causative event. Gene supply is the delivery of a gene that can prevent or arrest disease progression without being directly implicated in the disease pathogenesis. To this end, one of the most efficient and safe retinal gene delivery vehicles derives from the small adeno-associated virus (AAV). We review studies on AAV-mediated gene supply of: neurotrophic/antiapoptotic factors to prevent retinal neurons degeneration, and anti-angiogenic molecules to inhibit retinal neovascularization. Successful gene supply may represent a one-fit-all treatment for inherited and acquired blinding diseases.