Epigenetic Modifications and Potential New Treatment Targets in Diabetic Retinopathy

Figure 4

RAGE-dependent metabolic memory. RAGE also contributes to the establishment of the metabolic memory. Hyperglycemia-induced ROS formation leads to the production of methylglyoxal, which in turn induces the expression of RAGE and its ligands S100 and HMGB1. The production of RAGE ligands further activates RAGE, leading to NF-κB activation. NF-κB in turn induces (i) a chronic RAGE activation, leading to chronic neurovascular inflammation; (ii) epigenetic modification of gene expression. Both pathways are implicated in the metabolic memory.