National Clinical Research Center for Eye Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Fundus Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Immunol. 2022 Sep 2;13:942768. doi: 10.3389/fimmu.2022.942768. eCollection 2022.
Diabetic retinopathy (DR) is the leading cause of visual impairment and blindness among working-age people. Inflammation is recognized as a critical driver of the DR process. However, the main retina-specific cell type producing pro-inflammatory cytokines and its mechanism underlying DR are still unclear. Here, we used single-cell sequencing to identify microglia with metabolic pathway alterations that were the main source of IL-1β in STZ-induced DR mice. To profile the full extent of local metabolic shifts in activated microglia and to reveal the metabolic microenvironment contributing to immune mechanisms, we performed integrated metabolomics, lipidomics, and RNA profiling analyses in microglia cell line samples representative of the DR microenvironment. The results showed that activated microglia with IL-1β increase exhibited a metabolic bias favoring glycolysis, purine metabolism, and triacylglycerol synthesis, but less Tricarboxylic acid (TCA). In addition, some of these especially glycolysis was necessary to facilitate their pro-inflammation. These findings suggest that activated microglia with intracellular metabolic reprogramming in retina may contribute to pro-inflammation in the early DR.
糖尿病性视网膜病变（DR）是工作年龄段人群视力损害和失明的主要原因。炎症被认为是 DR 进程的关键驱动因素。然而，主要产生促炎细胞因子的视网膜特异性细胞类型及其在 DR 中的潜在机制仍不清楚。在这里，我们使用单细胞测序来鉴定在 STZ 诱导的 DR 小鼠中具有代谢途径改变的小胶质细胞，其是 IL-1β 的主要来源。为了描述激活的小胶质细胞中局部代谢变化的全貌，并揭示有助于免疫机制的代谢微环境，我们对代表 DR 微环境的小胶质细胞系样本进行了代谢组学、脂质组学和 RNA 谱分析的综合分析。结果表明，具有增加的 IL-1β 的激活小胶质细胞表现出有利于糖酵解、嘌呤代谢和三酰基甘油合成的代谢偏向，但三羧酸（TCA）较少。此外，其中一些特别是糖酵解对于促进它们的促炎作用是必要的。这些发现表明，视网膜中具有细胞内代谢重编程的激活小胶质细胞可能有助于早期 DR 中的促炎作用。
