Defensins and Corneal Wound Healing

防御素和角膜伤口愈合

• 批准号: 6641231
• 负责人: ALISON M MCDERMOTT
• 金额: $ 22.13万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6641231
• 关键词: antibody formation; cell migration; cell proliferation; cornea; corneal epithelium; cytokine; defensins; eye injury; fibroblasts; fluorimetry; growth factor; human tissue; immunofluorescence technique; organ culture; polymerase chain reaction; protein biosynthesis; statistics /biometry; western blottings; wound healing

DESCRIPTION (provided by applicant): Damage to the cornea compromises its important optical and protective functions; rapid repair is therefore critical. However, the mechanisms and factors orchestrating wound healing are unclear. A better understanding of the process is essential to our ability to improve and regulate corneal repair after accidental or surgical injury and in diseases such as recurrent erosion syndrome and diabetes where the integrity of the cornea is compromised. The overall goal of this project is to determine if and how defensins participate in corneal wound healing. Defensins are peptides best known for their antimicrobial activity but whose functional repertoire also includes mitogenic, chemoattractant and signaling properties. Two types of defensin are available to the cornea, alpha-defensins are present in tears and neutrophils recruited after injury and beta-defensins are produced in situ by corneal epithelial cells. Our overlying hypothesis is that alpha and beta defensins promote corneal wound healing. We hypothesize that they do so by stimulating corneal epithelial cell and fibroblast migration, proliferation and production of cytokines/growth factors. Furthermore, we hypothesize that cytokines produced after epithelial injury upregulate the expression of endogenous epithelial defensins which are then available in sufficient quantities to exert a physiological effect. Human corneal epithelial cells and fibroblasts and human corneas in organ culture will be utilized to address the following hypotheses: Specific Aim 1: Hypothesis: alpha and beta defensins stimulate human corneal epithelial cell and fibroblast migration and proliferation. Specific Aim 2: Hypothesis: alpha and beta defensins upregulate the production of cytokines and growth factors by human corneal epithelial cells and fibroblasts. Specific Aim 3: Hypothesis: Expression of endogenous beta-defensin 2 is upregulated after injury in response to an increase in cytokines. Specific Aim 4: Hypothesis: alpha and beta defensins stimulate re-epithelialization in wounded human corneas. The results of these studies will help delineate the as yet unidentified role of defensins in corneal wound healing and restoration of normal corneal function.

描述（由申请人提供）：对角膜的损害损害其 重要的光学和保护功能；因此，快速修复至关重要。 但是，尚不清楚修复伤口愈合的机制和因素。一个 更好地了解过程对于我们提高和提高能力至关重要 在意外或手术损伤和疾病中调节角膜修复 例如复发性侵蚀综合征和糖尿病的完整性 角膜被妥协。 该项目的总体目标是确定是否以及如何防御素 参加角膜伤口愈合。防御素是最著名的肽 它们的抗菌活性，但其功能曲目也包括 有丝分裂，化学吸引剂和信号传导特性。两种类型的防御素是 可用于角膜，α-防御素出现在眼泪和中性粒细胞中 受伤后招募和β-防御素是由角膜原地生产的 上皮细胞。我们上覆的假设是Alpha和Beta Defensin 促进角膜伤口愈合。我们假设他们通过刺激这样做 角膜上皮细胞和成纤维细胞迁移，增殖和生产 细胞因子/生长因子。此外，我们假设细胞因子 上皮损伤后产生的内源性表达 上皮防御素，然后以足够数量的速度使用 生理效应。 人角膜上皮细胞，成纤维细胞和器官中的人角膜 文化将用于解决以下假设： 特定目的1：假设：α和β防御素刺激人角膜 上皮细胞和成纤维细胞迁移和增殖。 特定目的2：假设：α和β防御素上调生产 人角膜上皮细胞和生长因子的细胞因子和生长因子 成纤维细胞。 特定目的3：假设：内源性β-防御素2的表达是 受伤后因细胞因子的增加而上调。 特定目标4：假设：α和β防御素刺激 受伤的人角膜重新上皮化。 这些研究的结果将有助于描述尚未确定的角色 在角膜伤口愈合和正常角膜的恢复中的防御素 功能。