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

点击翻译按钮获取中文摘要

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.