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<p>Myopia is a common refractive error with high prevalence; its pathogenesis is poorly understood. Scleral single-cell RNA sequencing is used to determine whether there is an association between phenotypic heterogeneity of scleral fibroblasts and form-deprivation myopia in male mice. The number of unique <i>Wnt5a</i>-positive scleral fibroblasts is markedly lower in the form-deprived eyes, specifically in the temporal inner peripapillary sclera. Inhibition of <i>Wnt5a</i> expression by injection of sh<i>Wnt5a</i>-AAV within Tenon’s capsule causes increased myopia progression, while decreasing COL1A1 protein content and collagen fibril diameter. Integrating scleral bulk RNA-seq data from sh<i>Wnt5a</i>-AAV injected male mice with data from scleral single-cell RNA sequencing in form-deprivation myopia mice, implicates the <i>Sparc</i> gene as a key downstream target of the Wnt5a signalling pathway. Tenon’s capsule injection of sh<i>Sparc</i>-AAV induces myopia, decreases scleral COL1A1 content, and reduces collagen fibril diameter. These results demonstrate that scleral-specific fibroblasts manifesting high <i>Wnt5a</i> expression (<i>Wnt5a</i><sup>hi</sup> fibroblast) modulate homeostasis of the extracellular matrix, thus promoting myopia progression.</p>

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Decreased scleral Wnt5ahi fibroblasts exacerbate myopia progression by disrupting extracellular matrix homeostasis in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月16日

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  • He Zhu,
  • Wei Chen,
  • Xuemei Ling,
  • Shiming Jiao,
  • Le Yu,
  • Huihui Liu,
  • Mengyi Ding,
  • Fan Zhang,
  • Yixin Zhou,
  • Yulu Pan,
  • Zhonglou Zhou,
  • Jia Qu,
  • Fei Zhao,
  • Fuxin Zhao,
  • Xiangtian Zhou

摘要

Myopia is a common refractive error with high prevalence; its pathogenesis is poorly understood. Scleral single-cell RNA sequencing is used to determine whether there is an association between phenotypic heterogeneity of scleral fibroblasts and form-deprivation myopia in male mice. The number of unique Wnt5a-positive scleral fibroblasts is markedly lower in the form-deprived eyes, specifically in the temporal inner peripapillary sclera. Inhibition of Wnt5a expression by injection of shWnt5a-AAV within Tenon’s capsule causes increased myopia progression, while decreasing COL1A1 protein content and collagen fibril diameter. Integrating scleral bulk RNA-seq data from shWnt5a-AAV injected male mice with data from scleral single-cell RNA sequencing in form-deprivation myopia mice, implicates the Sparc gene as a key downstream target of the Wnt5a signalling pathway. Tenon’s capsule injection of shSparc-AAV induces myopia, decreases scleral COL1A1 content, and reduces collagen fibril diameter. These results demonstrate that scleral-specific fibroblasts manifesting high Wnt5a expression (Wnt5ahi fibroblast) modulate homeostasis of the extracellular matrix, thus promoting myopia progression.