Mechanisms of Corneal Nerve Repair

角膜神经修复机制

• 批准号: 8511655
• 负责人: Mark I Rosenblatt
• 金额: $ 40.14万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8511655
• 关键词: Biochemical; Biological Assay; Biological Models; Blindness; Blinking; Chemical Injury; Cornea; Corneal Injury; Data; Defect; Dependence; Development; Dose; Dry Eye Syndromes; Epithelial; Esthesia; Event; Family member; Growth; Growth Factor; Health; Human; Human body; Immunohistochemistry; In Vitro; Infection; Injury; Keratitis; Keratopathy; Knockout Mice; Lead; Lentivirus Vector; Ligands; Lymphangiogenesis; Measures; Mediating; Mediator of activation protein; Modeling; Molecular; Monitor; Natural regeneration; Nerve; Nerve Regeneration; Neurons; Pathway interactions; Pattern; Perforation; Peripheral; Process; Recovery; Regulation; Role; Signal Pathway; Signal Transduction; Small Interfering RNA; Specificity; Structure of trigeminal ganglion; Techniques; Tissues; Trauma; Trigeminal System; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor B; Vascular Endothelial Growth Factor Receptor; Vascular Endothelial Growth Factors; Western Blotting; angiogenesis; arm; corneal epithelium; corneal repair; corneal surgery; density; in vivo; in vivo Model; inhibitor/antagonist; melting; neurogenesis; neuronal growth; neuronal patterning; neuronal survival; neutralizing antibody; novel; prevent; public health relevance; receptor; receptor expression; repaired; response

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.

描述（由申请人提供）：角膜是人类神经支配最密集的组织。周围角膜神经在受伤后会再生。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发生的信号通路不同。目标 A 将表征 VEGF 和 VEGF 受体的表达，并鉴定在体外和体内介导 VEGF 依赖性神经发生的受体。目标 B 将表征 VEGF 对 2 个损伤模型中神经再生的影响，而目标 C 将研究造成这些影响的途径。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。 公共卫生相关性：损伤后角膜神经需要适当再生，以防止发生潜在致盲的神经营养性角膜炎。该应用将研究已明确表征的 VEGF 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。