Augmentation of scleral glycolysis promotes myopia through histone lactylation
CELL METABOLISM(2024)
摘要
Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation(FMT). Scleral hypoxia is a significant factor contributing to myopia, but how hypoxia induces myopia ispoorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the sclera. Promotion of scleralglycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or lactateproduction eliminated or inhibited FMT and myopia. Mechanistically, increasing scleral glycolysis-lactatelevels promoted FMT and myopia via H3K18la, and this promotedNotch1expression. Genetic analyses iden-tified a significant enrichment of two genes encoding glycolytic enzymes,ENO2andTPI1. Moreover,increasing sugar intake in guinea pigs not only induced myopia but also enhanced the response to myopiainduction via the scleral glycolysis-lactate-histone lactylation pathway. Collectively, we suggest that scleralglycolysis contributes to myopia by promoting FMT via lactate-induced histone lactylation.
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