Unknown intraocular metabolic pathway leading to pro-inflammatory microglial activation

The term refers to the complex and often poorly defined metabolic reprogramming that occurs within retinal microglia during the progression of ocular diseases such as diabetic retinopathy, age-related macular degeneration (AMD), and glaucoma. Under conditions of metabolic stress, hypoxia, or hyperglycemia, resident retinal microglia undergo a shift from oxidative phosphorylation to aerobic glycolysis (the Warburg effect), which is a prerequisite for their transition to a pro-inflammatory (M1-like) state. This metabolic switch leads to the accumulation of metabolites like succinate and lactate, which act as signaling molecules to further drive the production of pro-inflammatory cytokines such as IL-1β and TNF-α. While specific components of this process, such as the succinate receptor (SUCNR1) or glycolytic enzymes like PKM2, are being investigated as therapeutic targets, the overarching 'unknown pathway' represents a broad research objective to identify the precise molecular triggers of this immunometabolic shift. Therapeutic strategies currently focus on inhibiting glycolysis or modulating mitochondrial function to restore microglial homeostasis and prevent neuroinflammation-mediated retinal damage.

Other names

Retinal microglial immunometabolic reprogrammingMetabolic shift in activated retinal microgliaGlycolytic switch in ocular microgliaIntraocular immunometabolism

Inhibition of aerobic glycolysis (Warburg effect), modulation of the succinate/SUCNR1 axis, and suppression of the NLRP3 inflammasome pathway to prevent pro-inflammatory microglial polarization.