Mechanisms of Corneal Nerve Repair

描述（由申请人提供）：角膜是人类神经支配最密集的组织。损伤后角膜周围神经再生。我们的假设是VEGF是损伤后角膜神经再生的关键决定因素，并且介导神经发生的信号通路与介导血管生成的信号通路不同。目的A将表征VEGF和VEGF受体的表达，并在体外和体内鉴定介导VEGF依赖性神经发生的受体。Aim B将描述VEGF对2种损伤模型神经再生的影响，Aim C将研究这些影响的通路。我们将分析不同损伤后VEGF介导的神经发生是否存在差异激活。

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.