Mechanisms of Corneal Nerve Repair

角膜神经修复机制

• 批准号: 8289558
• 负责人: Mark I Rosenblatt
• 金额: $ 42.25万
• 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/8289558
• 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。周围角膜神经损伤后再生。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。目的研究血管内皮生长因子（VEGF）及其受体的表达，并在体内外鉴定介导VEGF依赖性神经发生的受体。目的B将在两种损伤模型中表征VEGF对神经再生的作用，而目的C将研究负责这些作用的途径。我们将分析在不同的损伤后是否存在VEGF介导的神经发生的差异激活。 公共卫生相关性：损伤后角膜神经的适当再生是防止潜在致盲性神经营养性角膜炎发展所必需的。本申请将研究一个新的作用，在角膜神经再生的VEGF信号通路，以开发新的技术，促进角膜修复。