Carvedilol activates nuclear factor E2-related factor 2/ antioxidant response element pathway to inhibit oxidative stress and apoptosis of retinal pigment epithelial cells induced by high glucose.

Diabetic retinopathy (DR) is the most prominent manifestation of diabetic microangiopathy and is a serious complication of diabetes. Despite extensive researches focusing on DR, treatment options for DR are still limited. Carvedilol (CAR) has vasodilatory, antioxidant stress and anti-inflammatory effects and poses a vital role in addressing the issue of diabetic complications. This paper attempts to explore this property of CAR and investigate into its effects on DR. First, ARPE-19 cells were treated with different concentrations of CAR and cells were induced with 30 mM high glucose (HG) to establish a DR cell model. Cell viability was assayed by cell counting kit-8 (CCK-8) with or without HG induction. Cellular inflammation and oxidative stress were evaluated by enzyme-linked immunosorbent assay (ELISA) and corresponding kits. The measurement of apoptosis levels was conducted by Terminal dUTP nick-end labeling (TUNEL) and Western blotting. The protein levels related to Nrf2/ARE signaling pathway were assessed by Western blotting. Finally, cellular inflammation, oxidative stress and apoptosis in ARPE-19 cells pretreated with Nrf2 inhibitor ML385 were tested again by the same methods. Results showed that under HG induction, CAR effectively improved ARPE-19 cell viability, inhibited cellular inflammation, oxidative stress, and apoptosis. Moreover, CAR activated Nrf2/ARE signaling pathway, which further suppressed cellular inflammation, oxidative stress, and apoptosis. Overall, CAR inhibited HG-induced oxidative stress and apoptosis in retinal pigment epithelial cells by activating Nrf2/ARE pathway.