Resveratrol (RSV) is used as a protective therapy against diabetic retinopathy. However, the mechanism(s) underlying this protective effect has not been fully elucidated. Bovine retinal capillary endothelial cells (BRECs), an in vitro model, were used to investigate the mechanism of RSV. Our results showed that high glucose induced significant cellular apoptosis in BRECs, which was accompanied by increased intracellular levels of reactive oxygen species (ROS) and cleaved caspase-3. The glucose-induced apoptosis and ROS elevation were both inhibited by RSV. High glucose was found to decrease the levels of phosphorylated AMP-activated protein kinase (p-AMPK), which was accompanied by increased levels of Sirt1 and PGC-1α. These changes were reversed by RSV. We also demonstrated that AMPK regulates the modulations of Sirt1 and PGC-1α using specific inhibitors of AMPK and Sirt1 and small interfering RNAs of PGC-1α. In summary, the current study demonstrates that RSV is effective against high glucose-induced cellular apoptosis and its action is exerted via the inhibition of ROS/AMPK/Sirt1/PGC-1α pathway.

Aim: To investigate the effects of high glucose (HG) medium on expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in cultured rat retinal Müller cells and to determine the signaling pathways mediating the effects.