Lactate metabolism and lactylation in ocular diseases

Abstract

Lactate, once considered a mere metabolic byproduct of anaerobic glycolysis, has undergone a paradigm shift in its biological significance. Emerging evidence now positions it as a central regulator of cellular metabolism, signaling, and disease pathophysiology across diverse tissues, including the retina and other ocular structures. The retina, as a highly metabolically active and oxygen-demanding tissue, presents a unique landscape for lactate dynamics. Its reliance on aerobic glycolysis leads to substantial lactate production even under normoxic conditions. This metabolic strategy, while ensuring rapid adenosine triphosphate generation, also positions lactate as both an energy currency and a signaling molecule, with significant implications for retinal homeostasis and diseases. This review summarizes current advances in understanding lactate metabolism and its newly discovered post-translational modification, lactylation, in the context of major ocular pathologies, including myopia, ocular melanoma, autoimmune uveitis, and retinal neovascularization. By bridging molecular mechanisms with clinical implications, we aim to illuminate lactate's dual roles as a metabolic substrate and an epigenetic modulator in ocular health and diseases.