Mechanisms of Ocular Immune Privilege in the Posterior Eye

后眼的眼部免疫特权机制

基本信息

批准号：
8047973
负责人：
Joan Stein-Streilein
金额：
$ 23.31万
依托单位：
SCHEPENS EYE RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2013-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Immune privilege is conserved in all species as a mechanism to provide immunoprotection for organs and tissues. Immune privilege allows for immune protection in the absence of inflammation. When immune privilege is compromised, the eye is at risk for immune inflammatory and autoimmune diseases such as uveitis. Immune privilege is a multi-layered process and even during experiment autoimmune uveitis, immune privilege is only transiently lost, and returns to prevent a reoccurrence of the disease (1). However, our studies show that retinal laser burn (RLB) in one eye caused an extended loss of ocular immune privilege in both the laser treated and non-treated eye (2). In this R21 project we would like to exploit these observations and analyze the mechanisms that led to the abrogation of immune privilege. We propose that RLB abrogates immune privilege by inducing changes to the retinal- pigmented epithelium (RPE) and its suppressor function which in turn leads to increased susceptibility to experimental autoimmune uveitis (EAU). Our research plan will 1.) Analyze how and what RPE suppression function is lost; 2.) Compare changes in the expression of candidate regulatory molecules on RPE that might change during or after RLB; 3.) Determine if there is increased susceptibility to autoimmune uveitis in mice after RLB. PUBLIC HEALTH RELEVANCE: This R21 application will determine (using state of the art cellular, molecular approaches) how experimental retinal laser burn abrogates immune privilege in the posterior eye. The knowledge gained from these studies will enhance our understanding of ocular immune homeostasis and may aid in the development of new therapies for restoration of the immune privileged status in eyes that suffer from trauma or inflammatory diseases such as autoimmune uveitis.

描述（由申请人提供）：免疫特权在所有物种中都是保守的，作为一种为器官和组织提供免疫保护的机制。免疫特权允许在没有炎症的情况下提供免疫保护。当免疫特权受到损害时，眼睛面临免疫炎症和自身免疫性疾病（例如葡萄膜炎）的风险。免疫特权是一个多层次的过程，即使在实验性自身免疫性葡萄膜炎期间，免疫特权也只是暂时丧失，然后会恢复以防止疾病复发 (1)。然而，我们的研究表明，一只眼睛的视网膜激光烧伤 (RLB) 会导致激光治疗和未治疗的眼睛长期丧失眼部免疫特权 (2)。在这个 R21 项目中，我们希望利用这些观察结果并分析导致废除免疫特权的机制。我们认为，RLB 通过诱导视网膜色素上皮 (RPE) 及其抑制功能的变化来消除免疫特权，从而导致实验性自身免疫性葡萄膜炎 (EAU) 的易感性增加。我们的研究计划将 1.) 分析 RPE 抑制功能如何以及何种程度丧失； 2.) 比较 RPE 上可能在 RLB 期间或之后发生变化的候选调节分子表达的变化； 3.) 确定 RLB 后小鼠对自身免疫性葡萄膜炎的易感性是否增加。公共健康相关性：该 R21 应用将确定（使用最先进的细胞、分子方法）实验性视网膜激光烧伤如何消除后眼的免疫特权。从这些研究中获得的知识将增强我们对眼部免疫稳态的理解，并可能有助于开发新疗法，以恢复患有外伤或炎症性疾病（如自身免疫性葡萄膜炎）的眼睛的免疫特权状态。