MicroRNA-137 regulates hypoxia-induced retinal ganglion cell apoptosis through Notch

Abstract

The apoptosis of retinal ganglion cells (RGCs) is a hallmark of several optic neuropathies. MicroRNAs (miRNAs) are recently identified regulators of various biological processes. However, the role of miRNAs in regulating RGC apoptosis remains largely unknown. We herein aimed to demonstrate that miR-137 acts as a hypoxia-responsive gene in RGCs that is downregulated under hypoxic conditions. It was observed that overexpression of miR-137 markedly aggravated hypoxia-induced cell apoptosis, whereas inhibition of miR-137 effectively protected RGCs against hypoxia-induced apoptosis. Hypoxia induced Notch1 expression and signaling activation, while blocking Notch signaling significantly aggravated hypoxia-induced cell apoptosis. Further data revealed that the pro-survival Akt signaling pathway was involved in miR-137-Notch signaling pathway-mediated RGC protection. Knockdown of Notch significantly reversed the effect of anti-miR-137 on RGC protection and Akt signaling activation. In addition, blocking Akt signaling also significantly abrogated the protective effect of anti-miR-137 on hypoxia-induced cell injury. Overall, the results of the present study demonstrated that miR-137 targets Notch1 expression, revealing a novel link between miR-137 and Notch signaling, and suggesting that a miR-137/Notch1 axis may serve as a potential molecular target for the treatment of hypoxia-induced retinal diseases.