Retinal ischemia, through the activation of hypoxia-inducible factor-1 (HIF-1) (Huang et al., 2015), determines an overproduction of vascular endothelial growth factor (VEGF), a key factor involved in both the progression of retinopathy towards PDR, and in DME development through phosphorylation of tight junction proteins such as occludin and zonula occludens-1 (Antonetti et al., 1999). The gene discussed is VEGFA; the disease is retinal ischemia.