VEGF-A isoforms and semaphorins in corneal nerve development and regeneration

神经纤维支配角膜，调节眨眼、撕裂和伤口愈合，它们还为角膜的动态平衡提供神经营养因子。因此，由于损伤或炎症造成的角膜神经损伤会导致角膜功能障碍。炎症还会导致血管和淋巴管进入角膜，而角膜通常没有血管来确保光学透明。因此，角膜新生血管模糊了视力。此外，它还增加了角膜移植后移植排斥的风险。不幸的是，目前还没有获得批准的恢复透明度的药物，而减少病理性血管形成的标签外治疗可能会加速神经退化，加剧上皮缺陷并进一步增加炎症，引发神经血管病理的恶性循环，最终可能导致失明。因此，找出在促进角膜神经再生的同时处理新生血管的治疗方法具有重要的临床意义。然而，对角膜神经-血管相互作用的了解不足阻碍了这一领域的进展。该项目将以在神经血管界面定义血管内皮生长因子和信号素信号的最新进展为基础，以(A)获得关于角膜神经发育和再生中新的分子和细胞机制的知识；(B)确定在不诱导病理性新生血管的情况下促进角膜神经再生的策略，以恢复角膜的透明度，从而恢复视力。

Nerve fibres innervate the cornea to regulate blinking, tearing and wound healing, and they additionally supply neurotrophic factors for corneal homeostasis. Corneal nerve damage, due to injury or inflammation, therefore causes corneal dysfunction. Inflammation also causes blood and lymphatic vessels ingrowth into the cornea, which is normally devoid of vasculature to ensure optical transparency. Corneal neovascularisation therefore obscures vision. Moreover, it increases the risk of graft rejection after corneal transplantation. Unfortunately, there are no approved drugs to restore transparency, and off-label treatments that reduce pathological vasculature can accelerate nerve degeneration to exacerbate epithelial defects and further increase inflammation, initiating a vicious circle of neurovascular pathology that may culminate in blindness. It is therefore of great clinical importance to identify treatments that tackle neovascularisation whilst promoting nerve regeneration in the cornea. However, a poor understanding of corneal nerve-vessel interactions has hampered progress in this area. This project will build on recent progress in defining VEGF and semaphorin signalling at the neurovascular interface to (a) acquire knowledge about novel molecular and cellular mechanisms in corneal nerve development and regeneration; (b) identify strategies that promote corneal nerve regeneration without inducing pathological neovascularisation to restore corneal transparency and therefore vision.