Complement System and the Eye

描述(申请人提供)：补语系统是一个主要组成部分 与生俱来的免疫力，与免疫系统并行或协同作用。 补体激活提供了一种有效的宿主防御机制 通过产生效应器分子，参与细胞的外来生物 死亡和免疫/炎症反应。因为它有很强的致炎性 几种破坏能力严格补充了调节蛋白 控制补体激活。这些蛋白质提供了一种识别系统 区分自体和非自体，从而限制对宿主组织的损害。这个 前房是免疫的特权部位和控制 补体在这个部位的激活在保护视力方面可能很重要。我们的 结果表明，四种补体调节蛋白即CRY、CD59、 MCP和DAF在正常大鼠眼内表达，其表达为 在实验性自身免疫性前葡萄膜炎(EAAU)期间上调。 此外，正常的人眼内液体中还含有一种尚未确定的55 KDA补体抑制蛋白。这些结果提供了证据： 补体调节系统存在于眼睛中，以保护眼组织免受 补体激活事件造成的破坏。身份识别和 眼睛中补体调节蛋白的特征将是一个主要的 眼内炎症及其保护机制的研究进展 眼睛。这些研究应该为补语的相关性提供洞察力 葡萄膜炎中的调节蛋白，可能在治疗上有用 抑制眼内炎症反应和组织损伤。具体的 这项建议的目的是： 1.补体调节蛋白在实验性自身免疫前部的作用 葡萄膜炎(EAAU)， 2.可溶性补体调节蛋白(S)抑制EAAU，以及 3.正常人体内存在的55 kDa补体抑制物的特性 房水/玻璃体。

DESCRIPTION (provided by applicant): The complement system is a major component of innate immunity and acts in parallel or in concert with the immune system. Complement activation provides an effective host defense mechanism against foreign organisms by generating effector molecules, which are involved in cell death and immune/inflammatory responses. Because of its potent inflammatory and destructive capabilities several complement regulatory proteins strictly control complement activation. These proteins provide a recognition system to distinguish self from non-self, thus limiting damage to host tissue. The anterior chamber of the eye is an immune privileged site and control of complement activation at this site may be important in preserving vision. Our results demonstrate that four complement regulatory proteins namely Crry, CD59, MCP and DAF are expressed within the normal rat eye and their expression is upregulated during experimental autoimmune anterior uveitis (EAAU). Furthermore, normal human intraocular fluid also contains a yet unidentified 55 kDa complement inhibitory protein. These results provide evidence that a complement regulatory system exists in the eye to protect ocular tissue from destruction by complement activating events. Identification and characterization of complement regulatory proteins in the eye would be a major advance toward the understanding of intraocular inflammation and protection of the eye. These studies should provide insights into the relevance of complement regulatory proteins in uveitis and may be therapeutically useful for suppressing intraocular inflammatory responses and tissue damage. The specific aims of this proposal are: 1. Role of complement regulatory proteins in experimental autoimmnune anterior uveitis (EAAU), 2. Suppression of EAAU by soluble complement regulatory protein(s), and 3. Characterization of 55 kDa complement inhibitor present in normal human aqueous humor/vitreous.