三叉神经眼支组成角膜感觉神经纤维，其损伤可引起角膜缘干细胞（LSCs）异常，导致致盲性神经营养性角膜病变（NK），但角膜感觉神经调控LSCs特性的机制尚不清楚。我们前期发现：去三叉神经支配引起角膜缘P物质（SP）缺失，N-cadherin、Wnt/β-catenin靶基因及LSCs标记表达下降，增殖分化细胞增多；干扰SP引起LSCs细胞N-cadherin和Wnt/β-catenin靶基因表达下降。本课题利用细胞及小鼠模型从以下几方面证实神经肽P物质通过N-cadherin/Wnt/β-catenin通路调控LSCs特性：角膜感觉神经纤维释放神经肽SP，调控LSCs特性；N-cadherin介导SP调控LSCs细胞Wnt/β-catenin靶基因表达。目的在于揭示角膜感觉神经调控LSCs特性的分子机制，为LSCs及其巢功能研究开启新的思路，为阐明NK病理机制及探索新的治疗靶点提供理论依据。

Eye branch of trigeminal nerve composes corneal sensory nerve fibers, and its damage causes dysfunction of corneal limbal stem cells(LSCs), resulting in blinding neurotrophic keratopathy(NK). However, the molecular mechanism of how corneal sensory nerve modulates the biological characteristics of LSCs remains unclear. Our previous study found that deprived innervation of trigeminal nerve resulted in a deficiency of neuropeptide substance P(SP) and decreased expression of N-cadherin and target genes of Wnt/β-catenin, along with decreased expression of LSCs marker in corneal limbus. The percentage of proliferating and differentiating cell raised. Interfering the function of SP in vitro led to decreased expression of N-cadherin and target genes of Wnt/β-catenin in LSCs. This study employs cell culture and mouse models to confirm that neuropeptide P modulates the biological characteristics of LSCs through the N-cadherin/Wnt/β-catenin pathway in the following aspects: corneal sensory nerve fibers release neuropeptide SP to modulate the characteristics of LSCs, and SP regulates the expression of Wnt/β-catenin target gene by the means of N-cadherin in LSCs. The purpose is to reveal the molecular mechanism of how corneal sensory nerve modulates the characteristics of LSCs, which would shed a light on the researches of LSCs and limbal niche and provide theoretical basis for exploring the pathological mechanism of NK and opening a new train of therapeutic targets.