Immunometabolism in uveitis: mechanisms and therapeutic implications

Uveitis is a major cause of blindness worldwide, characterized by complex immune dysregulation involving both innate and adaptive responses. Emerging evidence highlights immunometabolism—the interaction between immune function and cellular metabolism—as a major determinant of disease onset and progression. In uveitis, immune cells undergo metabolic reprogramming, which directly shapes their phenotype and effector functions. Proinflammatory Th17 cells and M1 macrophages predominantly rely on glycolysis, whereas T regulatory cells (Tregs) and M2 macrophages favor fatty acid oxidation and oxidative phosphorylation, thereby influencing the inflammatory balance. Local metabolic disturbances, including hypoxia, lactate accumulation, lipid dysregulation, and amino acid imbalance, further remodel the ocular microenvironment and sustain chronic inflammation. Central signaling pathways such as mTOR, AMPK , HIF-1α, and the NLRP3 inflammasome integrate metabolic cues with immune responses, offering novel therapeutic entry points. Preclinical studies indicate that targeting metabolic checkpoints with small molecules, amino acid modulators, or exosome-based strategies holds significant promise for restoring immune homeostasis. This review summarizes current advances in immunometabolism in uveitis, emphasizing mechanistic insights and translational opportunities, and highlights metabolism-targeted therapy as a potential paradigm shift for improving clinical outcomes. • Immunometabolism shapes immune cell functions in uveitis. • Metabolic reprogramming of Th17 and Tregs drives ocular inflammation. • Targeting metabolic checkpoints offers novel therapeutic strategies for uveitis.