Microglia in retinal angiogenesis and diabetic retinopathy

Abstract

Diabetic retinopathy has a high probability of causing visual impairment or blindness throughout the disease progression and is characterized by the growth of new blood vessels in the retina at an advanced, proliferative stage. Microglia are a resident immune population in the central nervous system, known to play a crucial role in regulating retinal angiogenesis in both physiological and pathological conditions, including diabetic retinopathy. Physiologically, they are located close to blood vessels and are essential for forming new blood vessels (neovascularization). In diabetic retinopathy, microglia become widely activated, showing a distinct polarization phenotype that leads to their accumulation around neovascular tufts. These activated microglia induce pathogenic angiogenesis through the secretion of various angiogenic factors and by regulating the status of endothelial cells. Interestingly, some subtypes of microglia simultaneously promote the regression of neovascularization tufts and normal angiogenesis in neovascularization lesions. Modulating the state of microglial activation to ameliorate neovascularization thus appears as a promising potential therapeutic approach for managing diabetic retinopathy. Graphical abstract

Single‐cell RNA sequencing in exploring the pathogenesis of diabetic retinopathy

“…In DR, microglia alter ligand expression patterns or secrete angiogenic factors to influence pathogenic angiogenesis and ECs can alter the microglia phenotype in turn. 78 Ben et al. 50 deployed a set of ligand–receptor paired interactions in STZ‐induced diabetic and control mice and found that the diabetes‐induced Csf1r‒Csf1 was significantly enriched in microglia and ECs.…”

“…In addition to inflammation, the activation and accumulation of microglia are also correlated with pathogenic angiogenesis in DR. 75,78 Although studies using OIR models have reported a switch from M1 polarised microglia in the early stage of neovascularisation towards M2 polarisa-tion in the late phase, 79 the specific phenotype of microglia exerting promotional or inhibitory effects is relatively unclear. He et al 51 performed single-cell RNA profiling on the retinal microglia of OIR mice and identified a subpopulation that highly expressed the necroptosis-related genes Rip3 and Mlkl.…”

“…In DR, microglia alter ligand expression patterns or secrete angiogenic factors to influence pathogenic angiogenesis and ECs can alter the microglia phenotype in turn. 78 Ben et al 50 deployed a set of ligand-receptor paired interactions in STZ-induced diabetic and control mice and found that the diabetes-induced Csf1r-Csf1 was significantly enriched in microglia and ECs. The following experiments verified that ECs secrete CSF1 which acted on the CSF1R of microglia to activate the MAPK signalling pathway, which elicits microglial differentiation and triggers the secretion of inflammatory factors (Figure 2).…”