Glutamine supplementation alleviates scleral remodeling in experimental myopia by restoring glutathione-associated redox homeostasis

Scleral extracellular matrix remodeling is a critical event in myopia progression, but the metabolic mechanisms involved remain incompletely defined. This study investigated whether glutamine regulates scleral remodeling in experimental myopia through glutathione-associated redox homeostasis. Form-deprivation myopia (FDM) was induced in guinea pigs, and scleral tissues were analyzed by DIA-based proteomics. Human scleral fibroblasts (HSFs) were cultured under glutamine-deficient conditions with or without glutamine supplementation. L-buthionine sulfoximine (BSO) and ferrostatin-1 (Fer-1) were used to assess the involvement of glutathione-dependent redox regulation and lipid peroxidation-associated injury. The effect of glutamine supplementation was further evaluated in FDM guinea pigs. FDM induced a significant myopic shift and axial elongation. Proteomic analysis revealed marked alterations in scleral metabolic pathways, including glycolysis, oxidative phosphorylation, glutathione metabolism, and amino acid biosynthesis. In HSFs, glutamine deprivation decreased COL1A1, SLC7A11, and GPX4 expression, increased MMP2 expression, enhanced ROS-associated signals, elevated Fe2+ and MDA levels, and reduced the GSH/GSSG ratio. Glutamine supplementation attenuated these abnormalities, whereas BSO weakened its protective effects. Fer-1 partially alleviated glutamine deprivation-induced redox imbalance and extracellular matrix remodeling. In vivo, glutamine supplementation attenuated FDM-induced myopic progression, improved posterior scleral morphology and collagen organization, restored COL1A1, SLC7A11, and GPX4 expression, reduced MMP2 expression, and partially corrected GSH/GSSG, MDA, and iron abnormalities. These findings suggest that glutamine supplementation alleviates experimental myopia-associated scleral remodeling by restoring glutathione-associated redox homeostasis and reducing lipid peroxidation-related injury.