Glycolysis-Histone Lactylation Crosstalk Drives TXNIP-NLRP3-Mediated PANoptosome Assembly and PANoptosis Activation Underlying Diabetic Retinopathy Pathogenesis.

ABSTRACT: Diabetic retinopathy (DR), a major cause of vision loss in adults, involves aberrant metabolism and inflammation. This study investigated the interplay between glycolysis, histone lactylation, and PANoptosis in DR using human retinal pigment epithelial (RPE) cells under high glucose and diabetic mouse models. Results demonstrated a positive feedback loop where enhanced glycolysis increased histone lactylation, which in turn further promoted glycolysis. This cycle activated the expression of thioredoxin interacting protein (TXNIP) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3), leading to PANoptosome formation and triggering PANoptosis, a coordinated cell death pathway contributing to DR pathology. Crucially, experiments manipulating TXNIP expression (via RNAi or

SUBMITTER: Xi X 

PROVIDER: S-EPMC12433895 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature