Abstract
The corneal limbus contains limbal epithelial stem cells, stromal stem cells (SSCs), and stromal cells (SCs), which collectively contribute to the regeneration and maintenance of corneal epithelial integrity and transparency. However, the functional relationship among these three cell types remains unclear. The aim of this study was to investigate their morphological characteristics, potential inter-cell-type transformation mechanisms, and age-related alterations in these processes in the mouse corneal limbus. Keratocan-positive stromal cells (keratocytes) were predominantly localized in the posterior cornea and exhibited telocyte features, including expression of CD34, PDGFRα, and NG2. In contrast, SCA-1- and CD90-positive stromal stem cells were primarily distributed in the anterior stroma, where they maintained contact with stromal processes and extended toward the epithelial basal layer. A subset displayed epithelial stem cell-like features, consistent with a mesenchymal–epithelial transition-like process within the limbal niche. Aging (to 2 years) in mice was associated with reduced SSC numbers and morphological alterations, suggesting a potential decline in niche-associated regenerative capacity. Together, these findings clarify the spatial organization and cellular interactions within the limbal microenvironment and provide a foundation for developing SSC-based strategies for ex vivo corneal epithelial regeneration.
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This work was supported in part by the Japan Agency for Medical Research and Development (AMED1041608) to Y.K.
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Supplementary Material 1: Three-dimensional view of the same cells as in Fig. 4cI–IX, d showing the contact or adhesion state between epithelial-side stromal stem and stromal cells in the corneal limbus. On the epithelial side, part of the stromal cell processes is indented, placing stromal stem cells on the epithelial basement membrane side. Stromal stem cells adhere to stromal cell processes via microprocesses in their cytoplasm.
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Maeda, M., Eguchi, A. & Kataoka, Y. Morphological characteristics of corneal stromal stem cells and their age-related decline. Sci Rep (2026). https://doi.org/10.1038/s41598-026-50744-3
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DOI: https://doi.org/10.1038/s41598-026-50744-3