Resveratrol protects retinal ganglion cell axons through regulation of the SIRT1-JNK pathway

Abstract

It is reported that Ischemia and reperfusion damage (I/R damage) can lead to retinal ganglion cell (RGC) death and neurodegeneration, which in turn can lead to irreversible vision loss. In this study, we sought to understand the neuroprotective effect of resveratrol, the important activator of sirtuin1 (SIRT1), on RGC survival in I/R damage model and the molecular mechanism that mediate this effect. Our results show that resveratrol could reverse axonal swelling, holes, and the chaos of the nucleus in axons of RGCs caused by I/R. At the same time, resveratrol could also reverse the activation of retinal astrocytes and the loss of RGCs caused by I/R. Resveratrol increased the expression of SIRT1 while decreasing the phosphorylation of N-terminal kinase (JNK). SP600125(JNK inhibitor) decreased the phosphorylation of JNK while increasing the expression of SIRT1, indicating that SIRT1 and JNK can interact with each other. Simultaneous administration of resveratrol and sirtinol (SIRT1 inhibitor) neither increased the expression of SIRT1 nor decreased the phosphorylation of JNK, indicating that resveratrol affects the phosphorylation of JNK by SIRT1. In total, our research shows that resveratrol treatment significantly reduces apoptosis and axonal degeneration of RGCs, and this protection is partly mediated through the SIRT1-JNK pathway.

Keywords: I/R damage; JNK; Optic nerve; Resveratrol; Retinal ganglion cells; SIRT1.