Myopia is a globally prevalent refractive eye disease, with abnormal axial elongation as its core structural feature, and scleral remodeling is the key terminal event driving axial elongation. Transforming growth factor-β(TGF-β), as a core cytokine regulating tissue remodeling, modulates the phenotype of scleral fibroblasts, extracellular matrix(ECM)metabolism, and tissue mechanical properties through a multi-signaling axis network, thereby playing a crucial role in myopic scleral remodeling. This article systematically summarizes the core signaling mechanisms of TGF-β-mediated scleral remodeling. As a core driver, TGF-β synergistically promotes scleral remodeling at both transcriptional regulatory and cellular mechanical levels through its two downstream core signaling axes, namely Smad and Rho/ROCK. Bone morphogenetic protein(BMP), an important member of the TGF-β superfamily and a key negative regulator of the core signaling axes, maintains scleral homeostasis by antagonizing the TGF-β/Smad signaling. Additionally, the TGF-β core signaling axes may crosstalk with pathways such as Wnt/β-catenin and PI3K/Akt. This article clarifies the core significance of the TGF-β-mediated signaling axis network in the progression of myopia, provides a systematic framework for understanding the molecular mechanisms of myopic scleral remodeling, and identifies research gaps in areas such as crosstalk molecules among signaling axes, stage-specific functions, and clinical translation. It also offers novel insights for the precise prevention, control, and targeted treatment of myopia.

南京中医药大学大学生创新训练项目(No.X202510315402); 南京中医药大学附属医院2025年度院级课题(2004)国自然培育专项(No.Y25069)