Abstract
Myopia development is closely associated with scleral tissue loss in both human and animal models. This research aimed to investigate the metabolic changes in the sclera of lens-induced myopic guinea pigs and explore the underlying mechanisms. Myopia was induced in 2-week-old pigmented guinea pigs by having them wear -20-diopter lenses for 10 days, with one eye designated as the lens-induced myopic eye and the other as the control. Dual-platform untargeted metabolomics was performed using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) to analyze the metabolic changes in the sclera. Validation of amino acid levels in the sclera was conducted via targeted metabolomics. Glycine intervention was carried out in both scleral fibroblasts and the lens-induced myopia guinea pig model to evaluate its effects on COL1A1 synthesis and myopia progression. After 10 days of lens-induced myopia, GC-MS and LC-MS analyses identified significant changes in 29 and 85 metabolites in the myopic sclera, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the downregulation of amino acid and pyrimidine metabolism pathways was crucial in myopia development. Targeted amino acid metabolomics confirmed that multiple amino acids were significantly reduced in the myopic sclera. Glycine deficiency reduced COL1A1 levels in scleral fibroblasts, and glycine supplementation significantly increased its content. Animal studies demonstrated that glycine gavage significantly inhibited axial elongation and refractive error increase in lens-induced myopic guinea pigs, increased COL1A1 content, and reversed the reduction of ferroptosis-related proteins GPX4 and FTH1. Several amino acids, including glycine, l-isoleucine, l-serine, and l-valine, were significantly reduced in the myopic sclera, along with a marked downregulation of amino acid and pyrimidine metabolism pathways. Glycine supplementation can increase COL1A1 content and inhibit myopia progression by reducing ferroptosis within the sclera, suggesting that glycine could serve as a potential therapeutic intervention for myopia.
Published Version
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