Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, South Korea.
Department of Anesthesiology and Pain Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea.
FASEB J. 2022 Dec;36(12):e22643. doi: 10.1096/fj.202200865R.
Dopamine is a neurotransmitter that mediates visual function in the retina and diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of blindness; however, the role of dopamine in retinal vascular dysfunction in DR remains unclear. Here, we report a mechanism of hyperglycemic memory (HGM)-induced retinal microvascular dysfunction and the protective effect of dopamine against the HGM-induced retinal microvascular leakage and abnormalities. We found that HGM induced persistent oxidative stress, mitochondrial membrane potential collapse and fission, and adherens junction disassembly and subsequent vascular leakage after blood glucose normalization in the mouse retinas. These persistent hyperglycemic stresses were inhibited by dopamine treatment in human retinal endothelial cells and by intravitreal injection of levodopa in the retinas of HGM mice. Moreover, levodopa supplementation ameliorated HGM-induced pericyte degeneration, acellular capillary and pericyte ghost generation, and endothelial apoptosis in the mouse retinas. Our findings suggest that dopamine alleviates HGM-induced retinal microvascular leakage and abnormalities by inhibiting persistent oxidative stress and mitochondrial dysfunction.
多巴胺是一种神经递质，可介导视网膜的视觉功能，糖尿病视网膜病变（DR）是糖尿病最常见的微血管并发症，也是失明的主要原因；然而，多巴胺在 DR 中视网膜血管功能障碍中的作用仍不清楚。在这里，我们报告了高血糖记忆（HGM）诱导的视网膜微血管功能障碍的机制，以及多巴胺对 HGM 诱导的视网膜微血管渗漏和异常的保护作用。我们发现，HGM 在血糖正常化后诱导持续的氧化应激、线粒体膜电位崩溃和分裂，以及黏附连接解体，随后导致小鼠视网膜血管渗漏。在人视网膜内皮细胞中，多巴胺处理和 HGM 小鼠的玻璃体内注射左旋多巴抑制了这些持续的高血糖应激。此外，左旋多巴补充改善了 HGM 诱导的周细胞变性、无细胞毛细血管和周细胞鬼影形成以及内皮细胞凋亡。我们的研究结果表明，多巴胺通过抑制持续的氧化应激和线粒体功能障碍来减轻 HGM 诱导的视网膜微血管渗漏和异常。
