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

• Published in: Experimental eye research 2020-11, Vol.200, p.108249-108249, Article 108249
• Main Authors: Wu, Yue, Pang, Yulian, Wei, Wei, Shao, An, Deng, Cong, Li, Xiongfeng, Chang, Haoyu, Hu, Piaopiao, Liu, Xuequn, Zhang, Xu
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Disease Models, Animal; Gene Expression Regulation; I/R damage; Ischemia - drug therapy; Ischemia - genetics; Ischemia - metabolism; JNK; Male; MAP Kinase Signaling System - drug effects; Optic nerve; Rats; Rats, Sprague-Dawley; Resveratrol; Resveratrol - pharmacology; Retinal Diseases - drug therapy; Retinal Diseases - genetics; Retinal Diseases - metabolism; Retinal ganglion cells; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; RNA - genetics; SIRT1; Sirtuin 1 - biosynthesis; Sirtuin 1 - genetics
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2020.108249

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. •Retinal I/R injury causes damage to both RGCs and their axons.•SIRT1 and JNK protein can interact with each other.•Resveratrol protected rat RGC axons damage by inhibiting phosphorylation of JNK proteins through SIRT1.