Berberine attenuates apoptosis in rat retinal Müller cells stimulated with high glucose via enhancing autophagy and the AMPK/mTOR signaling

[Display omitted] •High glucose (HG) induce primary Müller cell injury through apoptosis.•BBR exerts beneficial effects under HG conditions due to its anti-apoptotic activity.•BBR might reduce HG-induced apoptosis in Müller cell through enhancing the formation of autophagy.•BBR might enhance the formation of autophagy through activation of AMPK signaling pathway. Berberine (BBR) has beneficial effects on diabetes and the multiple complications of diabetes due to its anti-apoptotic activity; however, the effect of BBR on diabetic retinopathy and its mechanism of action have not been clarified. The present study investigated the effect of BBR on Müller cells stimulated with high glucose (HG). Primary retinal Müller cells were incubated with high glucose to induce cell apoptosis; cells were pretreated with the AMPK inhibitor compound C and the AMPK activator AICAR to further explore the role of the AMPK/mTOR signaling pathway in the anti-apoptotic action of BBR. Immunofluorescence was used to measure apoptosis and autophagy. Western blot analysis was employed to determine the levels of p-AMPK and p-mTOR, as well as apoptosis-related proteins and autophagy-related proteins in Müller cells. Our results showed that BBR attenuated apoptosis, up regulated Bcl-2 and down regulated Bax and caspase-3 expression; enhanced the formation of autophagy, elevated the expression of Beclin-1 and LC3II and activated the AMPK/mTOR signaling pathway in Müller cells under high glucose conditions compared with the control group. The effect of BBR was partly blocked by compound C and strengthened by AICAR. BBR may have therapeutic potential to protect Müller cells from high-glucose-inducing apoptosis through enhancing autophagy and activating the AMPK/mTOR signaling pathway.