A New Perspective on the Regulation of Microglia-Mediated Inflammation in Diabetic Retinopathy: Mechanisms of NLRP3 Inflammasome Activation and Therapeutic Strategies
TL;DR
The effects of diabetes on NLRP3 inflammasome activity and microglial activation are summarized and targeting the NLRP3 inflammasome axis might serve as a promising therapeutic approach for ameliorating microglia-mediated inflammation and pathological progression in DR.
Abstract
Diabetic retinopathy (DR) is among the most common complications of diabetes mellitus and is characterized by microangiopathy and neurodegeneration. Microglia constitute a resident immune population in the central nervous system (CNS) and play crucial roles in regulating retinal angiogenesis under both physiological and pathological conditions. Microglia become widely activated in DR and induce pathogenic angiogenesis by regulating the status of endothelial cells. Modulating the state of microglial activation to ameliorate neovascularization thus appears to be a promising therapeutic approach for managing DR. The NOD-like receptor protein 3 (NLRP3) inflammasome is a cytosolic multimeric complex that plays a significant role in innate immunity. After sensing injury, the NLRP3 inflammasome induces the secretion of inflammatory cytokines (including interleukin (IL)-1β and IL-18) and triggers a form of inflammatory cell death known as pyroptosis. Recently, the NLRP3 inflammasome has been found to be abundantly expressed in microglia and has been shown to play critical roles in diabetes-associated neuroinflammation. Here, we summarize the effects of diabetes on NLRP3 inflammasome activity and microglial activation. The regulatory mechanisms of NLRP3, as well as NLRP3-targeted therapeutic strategies in microglia, will be reviewed. Targeting the NLRP3 inflammasome axis might serve as a promising therapeutic approach for ameliorating microglia-mediated inflammation and pathological progression in DR.