Lactylation and oxidative stress in diabetic retinopathy: Emerging links among metabolic reprogramming, epigenetic regulation and therapeutic potential.

Abstract

Diabetic retinopathy (DR) is a leading cause of visual impairment and is characterized by progressive microvascular injury, neurovascular dysfunction, and sustained oxidative stress. Lactylation, a lactate-derived post-translational modification, may represent a mechanistic link between hyperglycemia-induced metabolic reprogramming and epigenetic regulation. In the diabetic retina, enhanced glycolysis and lactate accumulation promote aberrant histone and non-histone lactylation, thereby contributing to endothelial dysfunction, Müller cell activation, inflammatory cell death, ferroptosis, and pathological angiogenesis. These processes may amplify oxidative injury by reshaping inflammatory and angiogenic transcriptional programs, impairing antioxidant defenses, and disrupting mitochondrial homeostasis. This review synthesizes direct retinal evidence linking lactylation to DR-related phenotypes, evaluates redox-related findings from retinal and other diabetic complications, and discusses the emerging but not yet established relationship between lactylation and oxidative stress in DR.