Cross Talks between Oxidative Stress, Inflammation and Epigenetics in Diabetic Retinopathy
Renu A. Kowluru
Abstract
Diabetic retinopathy, one of the most devastating complications of diabetes, is a multifactorial progressing disease with a very complex etiology. Although many metabolic, molecular, functional and structural changes have been identified in the retina and its vasculature, the exact molecular mechanism of its pathogenesis still remains elusive. Sustained high-circulating glucose increases oxidative stress in the retina and also activates the inflammatory cascade. Free radicals increase inflammatory mediators, and inflammation can increase production of free radicals, suggesting a positive loop between them. In addition, diabetes also facilitates many epigenetic modifications that can influence transcription of a gene without changing the DNA sequence. Several genes associated with oxidative stress and inflammation in the pathogenesis of diabetic retinopathy are also influenced by epigenetic modifications. This review discusses cross-talks between oxidative stress, inflammation and epigenetics in diabetic retinopathy. Since epigenetic changes are influenced by external factors such as environment and lifestyle, and they can also be reversed, this opens up possibilities for new strategies to inhibit the development/progression of this sight-threatening disease.