The set of processes triggered by hyperglycemia, such as a formation of AEG, activation of PKC, and the polyol and hexosamine pathways, provoke oxidative stress, which are also reinforced by oxidative stress in a vicious circle, causing a continuous increase in reactive oxygen species (ROS) and the consequent activation of pathophysiological mechanisms underlying the progression of DR [34,35,36]. This evidence concerns the gene PRRT2 and Hyperglycemia.