Pasqualina Colella and Alberto Auricchio Pages 371 - 380 ( 10 )
Common blinding diseases that are currently untreatable include conditions characterized by progressive neuronal degeneration, such as retinitis pigmentosa, Leber congenital amaurosis or glaucoma, and 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.
AAV, apoptosis, gene therapy, neurotrophic factors, photoreceptors, retina, retinal degeneration, retinal neovascularization, retinitis pigmentosa, Leber congenital amaurosis, glaucoma, adeno-associated virus, retinal neovascu-larization, retinal ganglion cell, retinal pigment epithe-lium, Ocular neovascularization, age-related macular degeneration, proliferative diabetic retinopathy, gene replacement, gene augmentation, gene repro-gramming, gene repair, gene supply, gene addition, rhodopsin, electroreti-nograms, glial cell-derived neurotrophic factor, Mertk gene, epithelium-derived growth factor, LEDGF, NAME?, Bcl-XL, baculoviral IAP repeat-containing pro-tein-4, BIRC4, X-linked inhibitor of apoptosis, XIAP, dominant macular dystrophy, dominant adult vitelliform macular dystrophy, dominant cone-rod dystrophy, laser-photocoagulation, hypoxia
Telethon Institute of Genetics and Medicine (TIGEM) and Medical Genetics, Dept of Pediatrics, “Federico II” University, Naples, Italy.