Diabetic retinopathy: Focus on NADPH oxidase and its potential as therapeutic target

Diabetic retinopathy is a common complication of diabetes that affects the retina due to a sustained high blood sugar level. Recent studies have demonstrated that high glucose-driven oxidative stress plays an important role in the microvascular complications of retina in diabetes. Oxidative stress occurs due to the excess of reactive oxygen species, which causes oxidative damage to retina, leading to the leak of tiny blood vessels, or acts as signaling molecules to trigger neovascularization, resulting in new fragile vessels. NADPH oxidase (NOX) is a key enzymatic source of reactive oxygen species in the retina, and it is involved in the early as well as the advanced stage of diabetic retinopathy. To date, at least 7 NOX isoforms, including NOX1 to NOX5, dual oxidase1 and dual oxidase 2, have been identified. It has been shown that NOX isoforms exert different roles in the pathogenesis of diabetic retinopathy. Intervention of NOX by its inhibitors or modulators shows beneficial effect on improving the retinal functions in the models of diabetic retinopathy in vivo or in vitro. Thereby, NOX might be a potential target for the therapy of diabetic retinopathy. The present review focuses on the role of NOX, particularly the NOX isoforms, in promoting the development of diabetic retinopathy. In addition, NOX isoforms as potential targets for therapy of diabetic retinopathy are also discussed.