Corneal scarring associated with various corneal conditions is a leading cause of blindness worldwide. The present study aimed to test the hypothesis that corneal stromal stem cells have a therapeutic effect and are able to restore the extracellular matrix organization and corneal transparency in vivo. We first developed a mouse model of corneal stromal scar induced by liquid nitrogen (N₂) application. We then reversed stromal scarring by injecting mouse or human corneal stromal stem cells in injured cornea. To characterize the mouse model developed in this study and the therapeutic effect of corneal stromal stem cells, we used a combination of in vivo (slit lamp, optical coherence tomography, in vivo confocal microscopy, optical coherence tomography shear wave elastography, and optokinetic tracking response) and ex vivo (full field optical coherence microscopy, flow cytometry, transmission electron microscopy, and histology) techniques. The mouse model obtained features early inflammation, keratocyte apoptosis, keratocyte transformation into myofibroblasts, collagen type III synthesis, impaired stromal ultrastructure, corneal stromal haze formation, increased corneal rigidity, and impaired visual acuity. Injection of stromal stem cells in N₂‐injured cornea resulted in improved corneal transparency associated with corneal stromal stem cell migration and growth in the recipient stroma, absence of inflammatory response, recipient corneal epithelial cell growth, decreased collagen type III stromal content, restored stromal ultrastructure, decreased stromal haze, decreased corneal rigidity, and improved vision. Our study demonstrates the ability of corneal stromal stem cells to promote regeneration of transparent stromal tissue after corneal scarring induced by liquid nitrogen.

中文翻译：

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N2损伤后，角膜基质干细胞恢复透明性。

与各种角膜状况相关的角膜瘢痕形成是全世界失明的主要原因。本研究旨在检验假说角膜基质干细胞具有治疗作用，并能够在体内恢复细胞外基质的组织和角膜透明性。我们首先开发了一种由液氮（N ₂）应用程序。然后，我们通过在受伤的角膜中注射小鼠或人角膜基质干细胞来逆转基质瘢痕形成。为了表征在这项研究中开发的小鼠模型和角膜基质干细胞的治疗效果，我们结合使用了体内（裂隙灯，光学相干断层扫描，体内共聚焦显微镜，光学相干断层成像，剪切波弹性成像和光动力学跟踪响应）和离体（全场光学相干显微镜，流式细胞仪，透射电子显微镜和组织学）技术。获得的小鼠模型具有早期炎症，角膜细胞凋亡，角膜细胞转化为成肌纤维细胞，III型胶原合成，基质超微结构受损，角膜基质雾度形成，角膜刚度增加和视敏度降低的特征。₂受伤的角膜导致与角膜基质干细胞迁移和受体基质生长相关的角膜透明性改善，无炎症反应，受体角膜上皮细胞生长，III型胶原基质含量减少，基质超微结构恢复，基质雾度降低，降低角膜僵硬，并改善视力。我们的研究证明了液氮诱导的角膜瘢痕形成后，角膜基质干细胞具有促进透明基质组织再生的能力。