Mechanisms Contributing to Inhibition of Retinal Ganglion Cell Apoptosis by AMPK in Experimental Glaucoma.

Abstract

AMPK is AMP-activated protein kinase that plays a major role in regulating energy metabolism. AMPK has attracted widespread interest as a potential therapeutic target for neurodegenerative diseases. However, its effects on glaucoma remain unclear. Here, we established the oxygen-glucose deprivation/recovery (OGD/R) model and retinal ischemia-reperfusion injury (I/R) model to simulate the glaucomatous injury. Our results demonstrated that OGD/R induced apoptosis. Retinal I/R caused thinner retinas, retinal ganglion cells (RGCs) loss, and an increase in the number of apoptotic RGCs by using H-E staining, TUNEL staining, and immunofluorescence staining. A slight increase in phosphorylation-AMPK (p-AMPK) level and a significant upregulation in phosphorylated-mTOR (p-mTOR) level were detected in experimental glaucoma models. Activating AMPK led to the downregulation of p-mTOR, Bax, and cleaved-caspase 3, upregulation of Bcl-2 as well as inhibition of apoptosis. I/R induced the loss of RGCs and an increase in the number of apoptotic RGCs, which was markedly relieved by using AMPK activator. Inhibiting AMPK by Compound C reversed the effects, led to the inhibition of p-AMPK and the upregulation of p-mTOR as well as promoting apoptosis. These findings indicate that activating AMPK attenuates RGCs apoptosis in glaucoma models via inhibiting mTOR. This study suggests that AMPK may be a novel target for glaucoma treatment.