REGULATION OF TISSUE DAMAGE IN UVEITIS

葡萄膜炎组织损伤的调节

• 批准号: 2163929
• 负责人: NARSING A RAO
• 金额: $ 25.11万
• 依托单位: DOHENY EYE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-06-01 至 1997-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2163929
• 关键词: antioxidants; disease /disorder model; immunopathology; laboratory rabbit; laboratory rat; neuroprotectants; neutrophil; oxidative stress; retinal pigment epithelium; superoxides; tissue /cell culture; uveitis

Uveitis is one of the major causes of legal blindness in the United States. Animal models of uveitis indicate that tissue damage is caused by various chemical mediators, including reactive oxygen metabolites that are derived from the inflammatory cells that characterize this disease. Our preliminary studies revealed a unique phenomenon: In the presence of a soluble peptide(s) produced by retinal pigment epithelium (RPE), neutrophil generation of superoxide was suppressed. Also. histologic examination of human eyes enucleated for severe uveitis reveals preservation of choriocapillaris and the retina at the site of intact RPE, which is consistent with RPE protection of the choriocapillaris. Based on our preliminary data and the morphologic observations, we hypothesize that RPE cells generate a peptide (or peptides) that protects the retina and choriocapillaris in uveitis by down-regulating superoxide production. This hypothesis will be studied using cell cultures of RPE and a clinically relevant model of uveitis. We will test our hypothesis with the following Specific Aims: 1. Purify and characterize the RPE protective peptide (RPP). 2. Determine the presence of RPP in normal RPE. 3. Detect the presence of RPP during the acute and chronic phases of S- antigen induced uveitis (EAU). The results of this study would elucidate the role of RPE in the modulation of uveitis, and could potentially provide a new therapeutic approach to the management of this blinding disease.

葡萄膜炎是美国法定失明的主要原因之一 国家。葡萄膜炎的动物模型表明组织损伤是由 各种化学介质，包括活性氧代谢物 源自这种疾病特征的炎症细胞。我们的 初步研究揭示了一个独特的现象：在存在 视网膜色素上皮（RPE）产生的可溶性肽， 中性粒细胞超氧化物的产生受到抑制。还。组织学的 对因严重葡萄膜炎而摘除人眼的检查显示 在完整 RPE 部位保存脉络膜毛细血管和视网膜， 这与RPE对脉络膜毛细血管的保护是一致的。基于 根据我们的初步数据和形态学观察，我们假设 RPE 细胞产生保护视网膜的肽（或多种肽） 通过下调超氧化物的产生来治疗葡萄膜炎中的脉络膜毛细血管。这 将使用 RPE 细胞培养物和临床研究来研究假设 葡萄膜炎的相关模型。我们将用以下方法检验我们的假设 具体目标： 1. 纯化并表征 RPE 保护肽 (RPP)。 2. 确定正常 RPE 中是否存在 RPP。 3. 检测S-急性期和慢性期RPP的存在 抗原诱导的葡萄膜炎（EAU）。 本研究的结果将阐明 RPE 在 调节葡萄膜炎，并可能提供一种新的治疗方法 治疗这种致盲疾病的方法。