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Molecular and Cellular Aspects of Corneal Nerve Regeneration

角膜神经再生的分子和细胞方面

基本信息

批准号：
8883549
负责人：
Sandeep Jain
金额：
$ 55.61万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8883549
关键词：
Adherence Affect Anti-Inflammatory Agents Anti-inflammatory Award Binding Biological Availability Blindness Bone Marrow Bone Marrow Cells Cell membrane Cell physiology Cells Clinical Collagen Collagen Receptors Cornea Corneal Diseases Data Development Disease Disintegrins Extracellular Matrix Eye diseases Functional disorder Growth Growth Cones Health Hematopoietic ITGAM gene Immigration Immune In Situ In Vitro Infiltration Integrin Binding Integrins Interleukin-10 Investigation Keratitis Keratoplasty Knowledge Lasers Lead Link Molecular Mus Mutate Myelogenous Myeloid Cells Natural regeneration Nerve Nerve Regeneration Neurites Neurons Nitric Oxide Operative Surgical Procedures Ophthalmology Peptides Phenotype Proteins RGD (sequence)Recombinants Research Semaphorin-1 Semaphorins Signal Transduction Structure of trigeminal ganglion Supplementation Suppressor-Effector T-Lymphocytes Surface System Therapeutic Intervention Transgenic Mice arginase base combinatorial cytokine eye dryness ganglion cell in vivo keratomileusis migration mutant nerve transection neurite growth novel therapeutics paracrine practical application receptor reinnervation research study response

项目摘要

DESCRIPTION (provided by applicant): Corneal nerve dysfunction forms the pathophysiological basis of ocular diseases, such as neurotrophic keratitis and dry-eye disease. Ophthalmic surgical procedures such as keratoplasty and laser-assisted in situ keratomileusis transect corneal nerves and may cause their dysfunction. The mechanisms responsible for corneal nerve regeneration have yet to be fully determined, and they constitute a high-priority need in the field of Ophthalmology. This proposal builds upon our research findings generated during the K08 award period. Our key finding was that Sema7a promotes nerve regeneration in the cornea and causes infiltration of myeloid cells. We propose to explore our hypothesis that Sema7a acts on neurites and infiltrating immature myeloid cells (which we call YFP-MDSCs) in the cornea to promote neuroregeneration, thus linking neuronal and myeloid systems. We will determine the mechanism of neurotrophic actions of myeloid cells that infiltrate the cornea and how Sema7a affects their actions (Aim A). We will determine whether corneal cell membrane- bound Sema7a is shed in the extracellular matrix for paracrine actions on neurites and myeloid cells (Aim B). Finally, we will determine whether peptides spanning integrin and disintegrin motifs of Sema7a selectively affect neurite growth and myeloid cell function (Aim C). Investigations detailed in this proposal will generate new knowledge to help fill gaps that currently exist in our understanding of corneal nerve regeneration mechanisms and their molecular and cellular interactions which may lead to new therapies.

描述（由申请人提供）：角膜神经功能障碍是眼部疾病（如神经营养性角膜炎和干眼病）的病理生理学基础。眼科手术如角膜移植术和激光辅助原位角膜磨镶术会切断角膜神经，并可能导致其功能障碍。负责角膜神经再生的机制尚未完全确定，它们构成了眼科领域的高度优先需求。本提案基于我们在K 08授予期间产生的研究成果。我们的关键发现是Sema 7a促进角膜神经再生并导致骨髓细胞浸润。我们建议探索我们的假设，即Sema 7a作用于角膜中的神经突和浸润的未成熟骨髓细胞（我们称之为YFP-MDSC）以促进神经再生，从而连接神经元和骨髓系统。我们将确定浸润角膜的骨髓细胞的神经营养作用机制以及Sema 7a如何影响它们的作用（目标A）。我们将确定角膜细胞膜结合的Sema 7a是否在细胞外基质中脱落以用于对神经突和骨髓细胞的旁分泌作用（Aim B）。最后，我们将确定跨越Sema 7a的整联蛋白和去整联蛋白基序的肽是否选择性地影响神经突生长和骨髓细胞功能（Aim C）。本提案中详细介绍的研究将产生新的知识，以帮助填补我们目前对角膜神经再生机制及其分子和细胞相互作用的理解中存在的空白，这可能导致新的治疗方法。