CAR AND THE ROLE OF AUTOIMMUNITY IN RETINAL DEGENERATION

拟议研究的长期目标是了解 自身免疫在引发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视网膜病变（CAR）， 副肿瘤综合征，作为研究的实验模型， 自身免疫参与感光细胞变性。 的 工作假说提出CAR源于自身免疫反应， 其针对肿瘤中发现的抗原或表位 和感光细胞。 这种分子模拟被认为 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。 本文所述的实验将使用从以下获得的自身抗体： 患有确定的视网膜疾病的患者，以检测视网膜 自身抗原 一旦抗原被表征， 可能的a）确定引发免疫原性的免疫原性来源， 自身免疫反应，B）提供关于以下的诊断信息 患者，如果发现支持视网膜疾病之间的相关性， 以及是否存在特异性自身抗体，以及c）进行调查 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 在CAR的诊断和某些癌症的早期检测中发挥重要作用。 不同的副肿瘤综合征可能有一个共同的 启动事件将有助于将研究重点放在早期肿瘤发展上。 最后，如果我们希望了解 并最终开发出感光细胞退化的治疗方法， 导致失明的主要原因 的识别 视网膜自身抗原可以引发实验性自身免疫反应， 动物的状况将是发展的重要一步， 更多型号。

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.