Cai Luwei, Xia Mengxue, Zhang Fang
National Clinical Research Center for Eye Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai 200080, China.
Antioxidants (Basel). 2024 Mar 29;13(4):423. doi: 10.3390/antiox13040423.
Diabetic retinopathy (DR) is the leading cause of visual impairment and blindness among the working-age population. Microglia, resident immune cells in the retina, are recognized as crucial drivers in the DR process. Microglia activation is a tightly regulated immunometabolic process. In the early stages of DR, the M1 phenotype commonly shifts from oxidative phosphorylation to aerobic glycolysis for energy production. Emerging evidence suggests that microglia in DR not only engage specific metabolic pathways but also rearrange their oxidation-reduction (redox) system. This redox adaptation supports metabolic reprogramming and offers potential therapeutic strategies using antioxidants. Here, we provide an overview of recent insights into the involvement of reactive oxygen species and the distinct roles played by key cellular antioxidant pathways, including the NADPH oxidase 2 system, which promotes glycolysis via enhanced glucose transporter 4 translocation to the cell membrane through the AKT/mTOR pathway, as well as the involvement of the thioredoxin and nuclear factor E2-related factor 2 antioxidant systems, which maintain microglia in an anti-inflammatory state. Therefore, we highlight the potential for targeting the modulation of microglial redox metabolism to offer new concepts for DR treatment.
糖尿病视网膜病变（DR）是工作年龄人群视力损害和失明的主要原因。小胶质细胞是视网膜中的常驻免疫细胞，被认为是DR进程中的关键驱动因素。小胶质细胞激活是一个严格调控的免疫代谢过程。在DR的早期阶段，M1表型通常从氧化磷酸化转变为有氧糖酵解以产生能量。新出现的证据表明，DR中的小胶质细胞不仅参与特定的代谢途径，还会重新排列其氧化还原系统。这种氧化还原适应支持代谢重编程，并提供了使用抗氧化剂的潜在治疗策略。在此，我们概述了近期关于活性氧参与情况以及关键细胞抗氧化途径所起不同作用的见解，这些途径包括NADPH氧化酶2系统，其通过AKT/mTOR途径促进葡萄糖转运蛋白4向细胞膜的易位从而促进糖酵解，以及硫氧还蛋白和核因子E2相关因子2抗氧化系统的参与情况，它们使小胶质细胞维持在抗炎状态。因此，我们强调了靶向调节小胶质细胞氧化还原代谢为DR治疗提供新概念的潜力。
