Mechanisms of Corneal Nerve Repair

描述(申请人提供)：角膜是人类中神经分布最密集的组织。损伤后角膜周围神经再生。我们的假设是，血管内皮生长因子是角膜损伤后神经再生的关键决定因素，介导神经发生的信号通路与介导血管生成的信号通路是不同的。目的研究血管内皮生长因子(VEGF)及其受体在体外和体内的表达，以确定介导血管内皮生长因子依赖性神经发生的受体。目的B将在两种损伤模型中描述血管内皮生长因子对神经再生的作用，而目的C将研究这些作用的途径。我们将分析不同损伤后是否存在不同激活的血管内皮生长因子介导的神经发生。 公共卫生相关性：需要在损伤后适当再生角膜神经，以防止潜在的致盲神经营养性角膜炎的发展。这一应用将探索具有良好特性的血管内皮生长因子信号通路在角膜神经再生中的新作用，以开发促进角膜修复的新技术。

DESCRIPTION (provided by applicant): The cornea is the most densely innervated tissue in humans. Peripheral corneal nerves regenerate follow injury. Our hypothesis is that VEGF is a critical determinant of corneal nerve regeneration after injury and that the signaling pathways which mediate neurogenesis are distinct from those which mediate angiogenesis. Aim A will characterize the expression of VEGF and VEGF receptors and identify the receptors which mediate VEGF-dependent neurogenesis in vitro and in vivo. Aim B will characterize effect of VEGF on the regeneration of nerves in 2 injury models, while Aim C will investigate the pathways responsible for these effects. We will analyze whether there exists a differential activation of VEGF mediated neurogenesis following different injuries. PUBLIC HEALTH RELEVANCE: Proper regeneration of corneal nerves after injury is needed to prevent the development of potentially blinding neurotrophic keratitis. This application will investigate a new role in corneal nerve regeneration for the well characterized VEGF signaling pathway in order to develop new techniques for promoting corneal repair.