OCULAR MUSCLE INVOLVEMENT BY MYASTHENIA GRAVIS

重症肌无力(MG)是由抗体引起的自身免疫性疾病 针对骨骼肌烟碱型乙酰胆碱受体。镁 仍然是视力受损的一个重要原因，尽管在 对其病理生理学的认识和治疗。的弱点 眼外肌(EOM)出现在约90%的肌无力患者和15%的 百分之百的肌无力患者只会表现出眼部症状。为什么是EOM 受影响比四肢肌肉更明显的是不了解。我们 假设EOM优先受到自身免疫过程的影响 因为它包含独特的表位，这些表位针对不同的目标 自身免疫介导的MG损伤。与四肢骨骼肌不同， 哺乳动物EOM含有多神经支配的纤维。小田贤一郎博士已经 从眼肌无力患者血清中鉴定出与其特异结合的抗体 至多神经支配纤维的终板区域。在第1阶段， 在训练计划中，我们将使用大田博士的抗体来筛查一名人类 构建EOMc DNA表达文库，鉴定与这些蛋白结合的融合蛋白 抗体。将对融合蛋白的DNA序列进行分析 与已知乙酰胆碱受体亚基和终板的相似性 蛋白质。在研究计划的第二阶段，这些病毒的致病性质 将通过开发一种酶联免疫吸附剂来评估蛋白质 眼肌无力和泛发性肌无力的检测及眼肌无力的动物模型。 研究计划为校长提供了理想的培训计划 调查员卡明斯基博士。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。这个项目的长期目标是 开发治疗重症肌无力的新方法，提高对重症肌无力的认识 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.