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Gene Gun Technology, Opioids, and Corneal Diseases

基因枪技术、阿片类药物和角膜疾病

基本信息

批准号：
6641233
负责人：
IAN S ZAGON
金额：
$ 14.05万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
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/6641233
关键词：
biotechnology cornea disorder corneal epithelium endogenous opioid evaluation /testing gene delivery system gene therapy genetic transcription histochemistry /cytochemistry homeostasis human tissue laboratory rat nonhuman therapy evaluation opioid receptor organ culture technology /technique development western blottings wound healing

项目摘要

DESCRIPTION: (Applicant's Abstract) The corneal epithelium modulates fluid transport for normal stromal hydration and corneal transparency, and serves as an anatomical and physiological barrier against ocular infection. This epithelium is in a constant state of renewal, and injury to this epithelium requires prompt resurfacing in order to re-establish visual function. Tools to achieve research and clinical applications to corneal diseases at the molecular level offer exciting avenues for advancement, but are stymied by the need for manipulating gene activity. Progress has been made in gene therapy through the development of a particle-mediated gene transfer delivery system (gene gun), a technique shown to be a rapid, highly efficient, and nontoxic method for transfection of genes both in vivo and in vitro. In this grant we propose to establish the gene gun as a valuable research tool in corneal epithelial biology, obtain preliminary information for the efficacy of the gene gun as a device for clinical treatment, and document the importance of the interaction of a native inhibitory peptide, opioid growth factor (OGF) with its receptor (OGFr) at the molecular level as a system regulating the homeostasis and healing of the ocular surface epithelium in humans and animals. The specific aims include: 1. Determine the importance of OGF-OGFr interfacing on maintenance of rat corneal epithelium by examining the consequences of molecular perturbation of OGF receptor gene and protein activity. 2. Define the role of an endogenous opioid system related to wound healing of the rat corneal epithelium following genetic alteration of the OGF receptor gene and protein expression in rat. 3. Ascertain the significance of OGF and OGFr function during wound healing of the human corneal epithelium using organ culture of tissues genetically modified to yield an excess or deficit of OGF receptor. Information derived from these studies will contribute to a breakthrough understanding of gene delivery systems to the corneal surface. Moreover, these investigations will simultaneously acquire invaluable knowledge about the molecular basis by which an endogenous opioid system relates to corneal epithelial homeostasis, and the restoration of corneal integrity following injury. Ultimately, such data can be employed to design molecular strategies to remedy visual dysfunction.

描述：（申请人摘要）角膜上皮调节流体正常基质水化和角膜透明度的运输，并作为防止眼部感染的解剖学和生理学屏障。这上皮细胞处于不断更新的状态，需要立即进行表面修复以重建视觉功能。工具来在分子水平上实现对角膜疾病的研究和临床应用水平提供了令人兴奋的晋升途径，但由于需要操纵基因活动基因治疗已经取得了进展，开发了一种颗粒介导的基因转移传递系统（基因枪），该技术被证明是一种快速、高效和无毒方法，体内和体外基因转染。在这一补助金中，我们建议建立基因枪作为角膜上皮细胞有价值的研究工具生物学，获得基因枪作为一种临床治疗器械，并记录相互作用的重要性阿片样生长因子（OGF）及其受体（OGFr）在分子水平上作为调节体内平衡的系统，人类和动物眼表上皮的愈合。具体目标包括：1.确定OGF-OGFr接口在大鼠角膜上皮的维持，通过检查 OGF受体基因和蛋白活性的分子扰动。2.定义内源性阿片系统在大鼠角膜创伤愈合中的作用 OGF受体基因和蛋白质遗传改变后的上皮在大鼠中的表达。3.明确OGF和OGFr功能的意义在人角膜上皮的伤口愈合过程中，经遗传修饰以产生过量或缺乏OGF受体的组织。从这些研究中获得的信息将有助于突破了解角膜表面的基因传递系统。而且这些调查将同时获得关于内源性阿片样物质系统与角膜相关的分子基础上皮内稳态，以及角膜完整性的恢复，损伤最终，这些数据可以用来设计分子策略，治疗视力障碍。