TXNIP Links Innate Host Defense Mechanisms to Oxidative Stress and Inflammation in Retinal Muller Glia under Chronic Hyperglycemia: Implications for Diabetic Retinopathy

Figure 10

A schematic summary of potential cellular responses by retinal Muller glia in chronic hyperglycemia and diabetes. The sequence of molecular events that retinal Muller cells react to chronic hyperglycemia include (i) sustained upregulation of TXNIP, (ii) an initial innate immune and UPR response to excess glucose metabolism and oxidative phosphorylation (ATP generation), (iii) oxidative stress (ROS/RNS generation) and a hypoxia-like response through ATP reduction, (iv) an induction of an autophagic-mitophagic pathway, and (v) ER-stress and inflammation. These cellular responses constitute intrinsic cell survival/defense mechanisms, which, under chronic cell stress and injury, may promote premature cell death and disease progression of DR.