Mesh : Animals Male Corneal Opacity / pathology Rats Cell Differentiation Corneal Keratocytes / metabolism Humans Disease Models, Animal Corneal Stroma / metabolism ultrastructure drug effects Visual Acuity Recovery of Function Cornea / pathology metabolism Rats, Sprague-Dawley

来  源:   DOI:10.1038/s41467-024-49008-3   PDF(Pubmed)

Abstract:
Intrastromal cell therapy utilizing quiescent corneal stromal keratocytes (qCSKs) from human donor corneas emerges as a promising treatment for corneal opacities, aiming to overcome limitations of traditional surgeries by reducing procedural complexity and donor dependency. This investigation demonstrates the therapeutic efficacy of qCSKs in a male rat model of corneal stromal opacity, underscoring the significance of cell-delivery quality and keratocyte differentiation in mediating corneal opacity resolution and visual function recovery. Quiescent CSKs-treated rats display improvements in escape latency and efficiency compared to wounded, non-treated rats in a Morris water maze, demonstrating improved visual acuity, while stromal fibroblasts-treated rats do not. Advanced imaging, including multiphoton microscopy, small-angle X-ray scattering, and transmission electron microscopy, revealed that qCSK therapy replicates the native cornea\'s collagen fibril morphometry, matrix order, and ultrastructural architecture. These findings, supported by the expression of keratan sulfate proteoglycans, validate qCSKs as a potential therapeutic solution for corneal opacities.
摘要:
利用来自人类供体角膜的静止角膜基质角膜细胞(qCSKs)的基质细胞疗法成为角膜混浊的有希望的治疗方法。旨在通过减少程序复杂性和供体依赖性来克服传统手术的局限性。这项研究证明了qCSK在雄性大鼠角膜基质混浊模型中的治疗效果,强调细胞传递质量和角膜细胞分化在介导角膜混浊分辨率和视功能恢复中的重要性。与受伤相比,静态CSKs治疗的大鼠在逃避潜伏期和效率方面表现出改善,莫里斯水迷宫中未经治疗的老鼠,显示改善的视力,而基质成纤维细胞治疗的大鼠则没有。先进的成像,包括多光子显微镜,小角度X射线散射,和透射电子显微镜,显示qCSK疗法复制天然角膜的胶原蛋白原纤维形态计量学,矩阵顺序,和超微结构结构。这些发现,由硫酸角质素蛋白聚糖的表达支持,验证qCSKs作为角膜混浊的潜在治疗解决方案。
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