CAR AND THE ROLE OF AUTOIMMUNITY IN RETINAL DEGENERATION

拟议研究的长期目标是了解 自身免疫在启动或加重视网膜变性中的作用 人类的疾病。 该提案主要关注癌症相关性视网膜病变(CAR)，这是一种 副肿瘤综合征作为研究卵巢癌的实验模型 自身免疫参与光感受器细胞退变。这个 工作假说认为CAR源于自身免疫反应 它是针对在两种肿瘤中发现的抗原或表位的 和感光细胞。这种分子模仿被认为是 几种自身免疫性疾病的基础，包括一些眼部炎症 人类的疾病。 这里描述的实验将使用从 患有明确视网膜疾病的患者，以便检测视网膜 自身抗原。一旦抗原被表征，它应该是 可能的a)以确定发起 自身免疫反应，b)提供有关的诊断信息 患者，如果研究结果支持视网膜疾病与 以及是否存在特定的自身抗体，以及c)调查 自身抗体影响视网膜变性的机制。 从这些实验中获得的结果可能被证明是一个重要的 参与CAR的诊断和某些癌症的早期发现。 不同的副肿瘤综合征可能共享一个共同的 启动活动将有助于集中研究早期肿瘤的发展。 最后，如果我们希望了解，还需要更多的实验模型 并最终开发出光感受器退化的治疗方法 这是这个国家导致失明的主要原因。身份的鉴定 可诱导实验性自身免疫的视网膜自身抗原 动物的条件将是发展的重要一步 其他型号。

The long-term objective of the proposed research is to understand the role of autoimmunity in initiating or exacerbating degenerative retinal disorders in humans. The proposal focuses primarily on cancer-associated retinopathy (CAR), a paraneoplastic syndrome, as an experimental model for studying the involvement of autoimmunity in photoreceptor cell degeneration. The working hypothesis proposes that CAR stems from an autoimmune response which is directed towards antigens or epitopes found in both the tumor and photoreceptor cells. Molecular mimicry of this sort is thought to underlie several autoimmune diseases, including some ocular inflammatory diseases in humans. The experiments described here will use autoantibodies obtained from patients with defined retinal diseases in order to detect retinal autoantigens. Once the antigens have been characterized, it should be possible a) to determine the immunogenic source that initiated the autoimmune response, b) to provide diagnostic information about patients, if findings support the correlation between a retinal disorder and the presence of specific autoantibodies, and c) to investigate mechanisms by which autoantibodies influence retinal degeneration. The results obtained from these experiments may prove to be an important part in the diagnosis of CAR and the early detection of some cancers. The finding that different paraneoplastic syndromes may share a common initiation event will help focus studies on early tumor development. Finally, more experimental models are needed if we hope to understand and eventually develop treatments for photoreceptor degeneration, the leading cause of blindness in this country. The identification of retinal autoantigens which can elicit an experimental autoimmune condition in animals would be an important step in the development of additional models.