Statins for prevention of diabetic-related blindness: a new treatment option?

Abstract

Diabetic retinopathy (DR), the most feared complication of diabetes, compromises vision and quality of life of approximately 50 million people worldwide, with its prevalence projected to double by 2025 [101]. DR, the leading cause of blindness in working-age adults in the USA, is characterized by early neurodegeneration, glial activation and vascular injury, which includes breakdown of the blood–retina barrier (BRB) and acellular capillary formation that eventually leads to retinal neo-vascularization and blindness (reviewed in [1]). Interestingly, early clinical trials including the Hoorn study, the Early Treatment Diabetic Retinopathy Study (ETDRS), and the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) [2–4] indicated that elevated serum lipids, including total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol, were associated with the presence of hard exudates and increased risk of DR. These results suggested that lipid-lowering therapies might be beneficial in the reduction of hard exudates and the associated vision loss in patients with DR. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that lower total and LDL-cholesterol in diabetic patients with or without cardiovascular disease. They inhibit the generation of mevalonate, a precursor of cholesterol, and inhibit isoprenoid synthesis. The beneficial effects of statins may extend beyond their cholesterol-lowering effects, to so-called pleiotropic effects, which include improving endothelial function, attenuating vascular and myocardial remodeling, inhibiting vascular inflammation and oxidation, and stabilizing atherosclerotic plaques. Statins’ pleiotropic effects are mainly attributed to blocking the isoprenylation of small GTPase proteins such as Rac-1, Rho and Cdc42 (reviewed in [5]). Although statins have reported benefits in diabetic microvascular diseases, their efficacy for DR has not been thoroughly investigated [6–8].