Melatonin inhibits Müller cell activation and pro-inflammatory cytokine production via upregulating the MEG3/miR-204/Sirt1 axis in experimental diabetic retinopathy

褪黑激素通过上调实验性糖尿病视网膜病变中的 MEG3/miR-204/Sirt1 轴来抑制 Müller 细胞活化和促炎细胞因子产生

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作者:Yuanyuan Tu, Manhui Zhu, Zhenzhen Wang, Kun Wang, Lili Chen, Wangrui Liu, Qin Shi, Qingliang Zhao, Yake Sun, Xiaoyu Wang, E Song, Xiaojuan Liu

Abstract

Diabetic retinopathy (DR) is the most common ocular complication caused by diabetes mellitus and is the main cause of visual impairment in working-age people. Reactive gliosis and pro-inflammatory cytokine production by Müller cells contribute to the progression of DR. Melatonin is a strong anti-inflammatory hormone, mediating the cytoprotective effect of a variety of retinal cells against hyperglycemia. In this study, melatonin inhibited the gliosis activation and inflammatory cytokine production of Müller cells in both in vitro and in vivo models of DR. The melatonin membrane blocker, Luzindole, invalidated the melatonin-mediated protective effect on Müller cells. Furthermore, melatonin inhibited Müller cell activation and pro-inflammatory cytokine production by upregulating the long noncoding RNA maternally expressed gene 3/miR-204/sirtuin 1 axis. In conclusion, our study suggested that melatonin treatment could be a novel therapeutic strategy for DR.

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