VEGFA and Hyperglycemia: In the early course of the disease, intracellular hyperglycemia leads to abnormal blood flow and increased vascular permeability due to reduced activity of vasodilators such as nitric oxide (NO), increased activity of vasoconstrictors like angiotensin II and endothelin-1, and alterations in permeability factors such as vascular endothelial growth factor (VEGF) (44).