OCULAR MUSCLE INVOLVEMENT BY MYASTHENIA GRAVIS

重症肌无力（MG）是一种自身免疫性疾病，由抗体引起 针对骨骼肌烟碱乙酰胆碱受体。MG 仍然是视力受损的一个重要原因， 治疗和了解其病理生理学。疲软 眼外肌（EOM）发生在约90%的肌无力患者和15 %的肌无力患者只会出现眼部症状。为什么EOM是 比四肢肌肉更显著的影响尚不清楚。我们 假设眼外膜优先受自身免疫过程的影响 因为它含有独特的表位， 自身免疫介导的MG损伤。与四肢骨骼肌不同， 哺乳动物眼外肌含有多种神经支配的纤维。小田健一郎博士 从眼肌无力患者血清中鉴定出的抗体， 到多神经支配纤维的终板区域。第1阶段 在训练计划中，我们将使用小田博士的抗体来筛选一个人 EOM cDNA表达文库，以鉴定结合这些蛋白的融合蛋白。 抗体的将分析融合蛋白的DNA序列， 与已知的乙酰胆碱受体亚单位和终板的相似性 proteins.在研究计划的第二阶段， 将通过开发酶联免疫吸附剂来评估蛋白质 眼MG和全身MG的测定以及眼MG的动物模型。 该研究计划为校长提供了一个理想的培训计划 调查员卡明斯基医生第一阶段用于教授基础分子 生物技术，而第二阶段导致这些方法的应用 一个重要的临床问题该项目的长期目标是 为MG开发新的治疗方式，并提高对 EOM功能。

Myasthenia gravis (MG) is an autoimmune disease, caused by antibodies directed at the skeletal muscle nicotinic acetylcholine receptor. MG continues to be a significant cause of impaired vision despite advances in treatment and understanding of its pathophysiology. Weakness of extraocular muscle (EOM) occurs in about 90 percent of myasthenics and 15 percent of all myasthenics will only manifest ocular signs. Why EOM is affected more prominently than extremity muscle is not understood. We hypothesize that EOM is preferentially affected by the autoimmune process because it contains unique epitopes which are differentially targeted for auto-immune mediated damage by MG. Unlike extremity skeletal muscle, mammalian EOM contains multiply-innervated fibers. Dr. Kenichiro Oda has identified antibodies from ocular myasthenics' sera whiCh bind exclusively to the endplate region of the multiply-innervated fibers. In Phase 1 of the training program, we will use Dr. Oda's antibodies to screen a human EOM cDNA expression library to identify fusion proteins which bind these antibodies. DNA sequences of the fusion proteins will be analyzed for similarities to known acetylcholine receptor subunits and endplate proteins. In Phase 2 of the research plan, the pathogenic nature of these proteins will be assessed by development of an enzyme-linked immunosorbent assay for ocular and generalized MG and animal model of ocular MG. The research program offers an ideal training program for the Principal Investigator, Dr. Kaminski. Phase 1 serves to teach fundamental molecular biological techniques, while Phase 2 leads to application of these methods to an important clinical problem. The long term goals of this project are to develop new treatment modalities for MG and improved understanding of the EOM function.