Fig. 5.

Abnormal DNA methylation contributes to DR through various pathogenic mechanisms. Diabetes is accompanied by metabolic disorders, including hyperglycemia, hyperhomocysteinemia, and hyperlipidemia. Dnmts and Tets are activated in the diabetic environment, and subsequent aberrant DNA methylation contributes to DR via oxidative stress, inflammation, and neovascularization. In addition, aberrant DNA methylation can be promoted by oxidative stress in turn, and its persistent status becomes a major driving force of metabolic memory. Dnmts, DNA methyltransferases; Tets, ten-eleven translocation dioxygenases; ROS, reactive oxygen species; VEGF, vascular endothelial growth factor; NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy