The Metaflammatory and Immunometabolic Role of Macrophages and Microglia in Diabetic Retinopathy

Emergent studies reveal the roles of inflammatory cells and cytokines in the development of diabetic retinopathy (DR), which is gradually portrayed as a chronic inflammatory disease accompanied by metabolic disorder. Through the pathogenesis of DR, macrophages or microglia play a critical role in the inflammation, neovascularization, and neurodegeneration of the retina. Conventionally, macrophages are generally divided into M1 and M2 phenotypes which mainly rely on glycolysis and oxidative phosphorylation, respectively. Recently, studies have found that nutrients (including glucose and lipids) and metabolites (such as lactate), can not only provide energy for cells, but also act as signaling molecules to regulate the function and fate of cells. In this review, we discussed the intrinsic correlations among the metabolic status, polarization, and function of macrophage/microglia in DR. Hyperglycemia and hyperlipidemia could induce M1-like and M2-like macrophages polarization in different phases of DR. Targeting the regulation of microglial metabolic profile might be a promising therapeutic strategy to modulate the polarization and function of macrophages/microglia, thus attenuating the progression of DR.