Diabetic retinopathy: important biochemical alterations and the main treatment strategies

Abstract Diabetes mellitus (DM) is a chronic metabolic disorder characterized by impaired glucose homeostasis, insulin resistance and hyperglycemia. Among its serious multi-systemic complications is diabetic retinopathy (DR), which develops slowly and often insidiously. This disorder, the most common cause of vision loss in working-age adults, is characterized by functional and morphological changes in the retina. It results from the exacerbation of ischemic and inflammatory conditions prompted by alterations in the blood vessels, such as the development of leukostasis, thickening of the basement membrane, retinal neovascularization and fibrovascular tissue formation at the vitreoretinal interface. The pathogenic alterations are usually triggered at the biochemical level, involving a greater activity in four pathways: the polyol pathway, the hexosamine pathway, the formation of advanced glycation end-products (AGEs), and the activation of protein kinase C (PKC) isoforms. When acting together, these pathways give rise to increased levels of reactive oxygen species (ROS) and decreased levels of endogenous antioxidant agents, thus generating oxidative stress. All current therapies are aimed at the later stages of DR and their application implies side effects. One possible strategy for preventing the complications of DM is to counteract the elevated superoxide production stemming from a high level of blood glucose. Accordingly, some treatments are under study for their capacity to reduce vascular leakage and avoid retinal ischemia, retinal neovascularization and macular edema. The present review summarizes the biochemical aspects of DR and of the main approaches for treating it.