角膜内皮细胞对维持角膜透明度发挥关键作用。人角膜内皮受损后难以再生，常引起大疱性角膜病变而致失明，目前主要治疗方法是角膜内皮移植术。猫和猴的角膜内皮再生能力与人类相似，而兔和鼠的角膜内皮受损后则可完全再生。我们的前期研究发现，兔角膜内皮细胞有很强的体内重编程能力，在损伤修复过程中，内皮细胞先转化为间充质细胞，在内皮缺损面愈合后再转化为内皮细胞，从而实现完全再生。本项目使用RNA-seq和蛋白组学分析方法筛选兔和猫角膜内皮损伤愈合的关键差异表达基因和信号通路。在此基础上，探讨角膜内皮损伤愈合过程中细胞微环境的变化及体内重编程的生物学事件，从体内外水平破解兔角膜内皮细胞重编程与再生的机制，并将这种机制应用到人的角膜内皮细胞损伤修复过程中，诱导人角膜内皮细胞的再生。本项目的实施将有助于发展新的角膜内皮损伤治疗方法。

Cornea endothelial cells (CECs) play pivotal role in maintaining the transparency of cornea. Human CECs could not regenerate after severe wounding and will cause bullous keratopathy which ultimately lead to blindness. Currently, the main therapy for bullous keratopathy is CECs transplantation. The in vivo regenerative capacity of CECs in cat and monkey is similar to that of humans. However, rabbit and rat CECs show prominent regenerative capacity after injury. In our previous study, we found that rabbit CECs have a strong capability of in vivo cell reprogramming. During the endothelial wound healing process, endothelial cells transformed into mesenchymal phenotype during the early stage, then transformed back to endothelial phenotype after closure of the wounding area with full regeneration. In the current study, we intend to screen the differentially expressed genes and signaling pathways between rabbit and cat CECs during corneal endothelial wound healing based on RNA-seq and proteomic analysis. Furthermore, we will investigate the micro-environment change and biological events involved in the corneal endothelial wound healing process. Based on this, we intend to unravel the mechanism of reprogramming and regeneration of rabbit corneal endothelium using in vivo and in vitro methods. After that, we will apply this machinery in human corneal endothelial wound healing process using ex vivo tissue culture model to induce the regeneration of human corneal endothelium. We hope this project may lay the foundation for development of new therapy for human corneal endothelial injury.