Nerve growth factor in diabetic retinopathy: beyond neurons

Diabetic retinopathy (DR), a major ocular complication of diabetes, is a leading cause of blindness in US working age adults with limited treatments. Neurotrophins (NTs), a family of proteins essential for growth, differentiation and survival of retinal neurons, have emerged as potential players in the pathogenesis of DR. NTs can signal through their corresponding tropomyosin kinase related receptor to mediate cell survival or through the p75 neurotrophin receptor with the co-receptor, sortilin, to mediate cell death. This review focuses on the role of NGF, the first discovered NT, in the development of DR. Impaired processing of proNGF has been found in ocular fluids from diabetic patients as well as experimental models. Evidence from literature and our studies support the notion that NTs appear to play multiple potential roles in DR, hence, understanding their contribution to DR may lead to promising therapeutic approaches for this devastating disease.