眼上皮细胞的病变常常引起光学功能丧失而致盲。申请人围绕成体干细胞稳态维持和眼组织再生医学进行研究，提出上皮细胞去分化引发异常化生的新机制（Cell，2011，共同第一作者）；发现决定角膜上皮干细胞命运的因子PAX6，成功利用诱导的皮肤上皮干细胞重建功能性角膜（Nature, 2014，第一作者; JBC, 2015，通讯作者）;明确晶状体上皮干细胞自我更新关键因子，实现人晶状体原位再生（Nature, 2016，共同第一作者）。目前，由角膜损伤等引发的基质纤维化、瘢痕形成致盲眼病主要以角膜移植为治疗手段，但面临供体严重不足、术后免疫排斥等问题。我们在前期研究中发现，角膜上皮细胞具有调控基质透明性的功能，但其具体机制尚不清楚。本项目拟深入研究角膜上皮细胞和基质细胞转录基因组及互作网络，探寻可抑制基质细胞纤维化的细胞因子，以期减少角膜基质损伤的瘢痕化，恢复角膜透明性。

Pathological changes of ocular epithelial cells usually lead to optical defect and vision loss. The applicant has focused on adult stem cell homeostasis and eye regeneration, and proposed a new source of epithelial metaplasia (Cell, 2011, co-first author); discovered PAX6 as the key factor of corneal epithelial cell-fate determination, reconstructed cornea by transplantation of PAX6-induced skin epithelial stem cells (Nature, 2014, first author; JBC, 2015, corresponding author); identified key factors regulating lens epithelial stem cell self-renewal, and regenerated human lenses with visual function in their natural environment (Nature, 2016, co-first author). Currently, the primary treatment of corneal stromal fibrosis and scarring caused by corneal damage is corneal transplantation. However, due to severe shortage of donor cornea and transplant rejection, many patients are left waiting in blindness. Our preliminary results show that the corneal epithelial cells can control corneal clarity, but the underlying mechanism is still unclear. In this project, we aim to investigate the genome-wide transcriptional profiling and interaction of corneal epithelial cells and keratocytes, and determine the involvement of cytokines in inhibition of fibrosis. The goal is to find a new treatment for blindness caused by fibrosis of corneal stroma.