The conditioned medium from AC under high glucose conditions also inhibited the migration and capillary morphogenesis of retinal EC. Capillary morphogenesis was restored when astrocytes were incubated with NAC under high glucose conditions. Together, our results suggest that high glucose conditions affect proliferation, adhesion, and migration of retinal AC through increased oxidative stress and production of inflammatory mediators. The effect of diabetic conditions on the apoptosis of vascular cells including retinal AC has been subject of numerous studies. In the retina of diabetic rats, the rate of neuronal apoptosis was elevated compared with non-diabetic rats. However, the apoptosis rate of retinal AC in diabetic mice was similar to that of nondiabetic mice. These results are consistent with our observation that high glucose conditions did not increase the rate of apoptosis in retinal AC. Thus, apoptosis of retinal AC is not affected under high glucose conditions, unlike retinal pericytes. This may be attributed to specific activation of Nrf2 and enhanced expression of anti-oxidant enzymes in AC cultured under high glucose conditions, which does not occur in retinal pericytes. High glucose conditions elevated ROS levels and oxidative stress in retinal AC, and resulted in the activation of cellular defense mechanisms. Nrf2 is a transcription factor that regulates the expression of antioxidant enzymes including Prdx2 and HO-1 in response to oxidative stress. Oxidative stress also induces phosphorylation of Fyn kinase, which can increase phosphorylation of Nrf2 leading to its degradation. Here we showed that high glucose conditions increased p-Fyn levels in response to oxidative stress. However, we did not observe a significant difference in the total levels of Nrf2 in AC cultured under various glucose conditions. To activate transcription of antioxidant enzyme, Nrf2 is translocated into the nucleus and binds to a cis-acting antioxidant responsive element in antioxidant genes. High glucose conditions increased nuclear translocation of Nrf2 in retinal AC. These changes were concomitant with increased levels of antioxidant enzymes Prdx2 and HO-1. Heme oxygenase-1 is an BEZ235 PI3K inhibitor enzyme that responds to stress and the rate-limiting enzyme in heme catabolism. Induction of HO-1 in diabetic retinopathy has protective roles by anti-inflammatory, anti-apoptosis and antiproliferative effects. Prdx2 is a cellular peroxidase that reduces H2O2 and prevents inactivation of redox-sensitive signaling pathways. Prdx2 protects against apoptosis in retinal photoreceptor cells. Thus, up-regulation of antioxidant enzyme including Prdx2 and HO-1 might protect retinal AC against oxidative stress induced under high glucose conditions. However, recently a role for Nrf2 in increased oxidative stress and proinflammatory responses has been demonstrated through stimulation of transcription factor Kruppel-like factor 9 and activation of inflammasome and production of IL-1b. Whether Klf9 is expressed in retinal AC, and if its expression is regulated under high glucose conditions.