1. Academic Validation
  2. Integrated multi-omics reveals the activated retinal microglia with intracellular metabolic reprogramming contributes to inflammation in STZ-induced early diabetic retinopathy

Integrated multi-omics reveals the activated retinal microglia with intracellular metabolic reprogramming contributes to inflammation in STZ-induced early diabetic retinopathy

  • Front Immunol. 2022 Sep 2;13:942768. doi: 10.3389/fimmu.2022.942768.
Kangjia Lv 1 2 3 4 Hui Ying 1 2 3 4 Guangyi Hu 1 2 3 4 Jing Hu 1 2 3 4 Qizhi Jian 1 2 3 4 Fang Zhang 1 2 3 4
Affiliations

Affiliations

  • 1 National Clinical Research Center for Eye Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Shanghai Key Laboratory of Fundus Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract

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.

Keywords

Diabetic retinopathy; inflammation; metabolic reprogramming; microglia; multi-omics.

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