Retinal pigment epithelial cells are closely associated with the pathogenesis of diabetic retinopathy. The mechanism by which diabetes impacts retinal pigment epithelial cell function is of significant interest. Sirtuins are an important class of proteins that primarily possess nicotinamide adenine dinucleotide-dependent deacetylases activity and involved in various cellular physiological and pathological processes. Here, we aimed to examine the role of sirtuins in the induction of diabetes-associated retinal pigment epithelial cell dysfunction. High glucose and platelet-derived growth factor (PDGF) treatment induced epithelial–mesenchymal transition and the migration of retinal pigment epithelial cells, and decreased sirtuin-3 expression. Sirtuin-3 knockdown using siRNA increased epithelial–mesenchymal transition and migration of retinal pigment epithelial cells. In contrast, sirtuin-3 overexpression attenuated the effects caused by high glucose and PDGF on epithelial–mesenchymal transition and migration of retinal pigment epithelial cells, suggesting that sirtuin-3 deficiency contributed to retinal pigment epithelial cell dysfunction induced by high glucose and PDGF. Mechanistically, sirtuin-3 deficiency induced retinal pigment epithelial cell dysfunction by the overproduction of mitochondrial reactive oxygen species. These results suggest that sirtuin-3 deficiency mediates the migration of retinal pigment epithelial cells, at least partially by increasing mitochondrial oxidative stress, and shed light on the importance of sirtuin-3 and mitochondrial reactive oxygen species as potential targets in diabetic retinopathy therapy.

视网膜色素上皮细胞与糖尿病视网膜病变的发病机制密切相关。糖尿病影响视网膜色素上皮细胞功能的机制具有重要意义。Sirtuins 是一类重要的蛋白质，主要具有烟酰胺腺嘌呤二核苷酸依赖性脱乙酰酶活性，并参与各种细胞生理和病理过程。在这里，我们旨在检查sirtuins 在诱导糖尿病相关视网膜色素上皮细胞功能障碍中的作用。高葡萄糖和血小板衍生生长因子 (PDGF) 治疗诱导上皮间质转化和视网膜色素上皮细胞迁移，并降低 sirtuin-3 表达。使用 siRNA 敲低 Sirtuin-3 可增加视网膜色素上皮细胞的上皮间质转化和迁移。相反，sirtuin-3 过表达减弱了高糖和 PDGF 对视网膜色素上皮细胞上皮间质转化和迁移的影响，表明 sirtuin-3 缺乏导致高糖和 PDGF 诱导的视网膜色素上皮细胞功能障碍。从机制上讲，sirtuin-3 缺乏会通过线粒体活性氧的过度产生来诱导视网膜色素上皮细胞功能障碍。这些结果表明sirtuin-3缺乏介导视网膜色素上皮细胞的迁移，至少部分是通过增加线粒体氧化应激，