CANCER-ASSOCIATED RETINOPATHY

癌症相关视网膜病变

基本信息

批准号：
3266422
负责人：
CHARLES Edward THIRKILL
金额：
$ 18.74万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-07-01 至 1996-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3266422
关键词：
antigen antibody reaction autoimmune disorder calcium binding protein cancer complication complementary DNA enzyme linked immunosorbent assay gene expression human subject immunocytochemistry immunopathology laboratory rabbit laboratory rat molecular biology molecular cloning neoplasm /cancer genetics neoplasm /cancer immunology nucleic acid probes retina disorder small cell lung cancer tissue /cell culture tumor antigens uveitis vision disorders western blottings

antigen antibody reaction autoimmune disorder calcium binding protein cancer complication complementary DNA enzyme linked immunosorbent assay gene expression human subject immunocytochemistry immunopathology laboratory rabbit laboratory rat molecular biology molecular cloning neoplasm /cancer genetics neoplasm /cancer immunology nucleic acid probes retina disorder small cell lung cancer tissue /cell culture tumor antigens uveitis vision disorders western blottings

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项目摘要

Cancer Associated Retinopathies (CAR) occur most commonly in patients with small cell carcinoma of the lung (SCCL), although this phenomenon has also been encountered in patients with retinopathies associated with breast, colon, prostate and cervical carcinomas. CAR degenerations progress rapidly and are reported to manifest prior to the recognition of the causal cancer. Serum samples obtained from CAR patients have consistently demonstrated a specific antibody reaction with a 23 kDa retina protein which is now referred to as the retinal CAR antigen. The cloning of the cDNA corresponding to this antigen and its recognition as the photoreceptor molecule 'Recoverin' has identified an important link in the biological processes involved in these retinopathies. The molecular cloning of a cDNA of the same nucleic acid sequence from a cDNA library prepared from mRNA derived from a culture of SCCL identifies an immunological 'Cancer Connection' which could be responsible for initiating an autoimmune retinopathy. These finding introduce the hypothesis that, in some cancer associated retinopathies, 'Molecular Mimicry' is the cause of the collective indications of retinal hypersensitivity. The long term goals of this proposal are to investigate the pathogenesis of CAR. To ascertain the significance of the 23 kDa retinal CAR antigen/antibody reaction to vision loss in CAR patients and determine if this immunological response is directly involved in the retinopathic events that occur in CAR or is it simply a marker which identifies the presence of a SCCL aberrantly expressing a distinctive retinal protein. The specific aims are to (a) evaluate the incidence of expression of the retinal CAR antigen in cultures of SCCL deposited in the ATCC as well as in primary cultures of SCCL originated from CAR patients, (b) investigate the immunological response of experimental animals to sensitization to the potentially uveitogenic retinal CAR antigen and specific peptide components of the molecule and (c) characterize the nature of the genes expressing the retinal CAR antigen and the corresponding antigenic component identified in the culture of small cell carcinoma of the lung. The study will use a combination of immunological and molecular biology techniques to determine if the indications of retinal hypersensitivity associated with CAR represent an example of immune-mediated vision loss resulting from antigenic cross-reactions.

癌症相关的视网膜病（CAR）最常见于患者尽管这种现象与视网膜病变有关的患者也遇到了乳房，结肠，前列腺和宫颈癌。汽车退化迅速进展，据报道在认识之前表现出来因果癌。从汽车患者获得的血清样品具有始终证明与23 kDa的特异性抗体反应视网膜蛋白现在称为视网膜抗原。这与该抗原相对应的cDNA的克隆及其识别为感光细胞分子“恢复蛋白”已经确定了一个重要的链接在这些视网膜病中涉及的生物过程中。这来自cDNA的相同核酸序列的cDNA的分子克隆从源自SCCL培养的mRNA制备的库可以识别免疫“癌症连接”，可能是负责的发起自身免疫性视网膜病。这些发现介绍了假设在某些癌症相关的视网膜病中，分子模仿是视网膜集体指示的原因高敏性。该提案的长期目标是研究发病机理汽车。确定23 kDa视网膜汽车的重要性汽车患者对视力丧失的抗原/抗体反应，并确定是否是否这种免疫反应直接参与视网膜病汽车中发生的事件，或者仅仅是标记的标记 SCCL的存在异常表达独特的视网膜蛋白。具体目的是（a）评估表达的发生率 SCCL培养物的视网膜抗原以及ATCC中的SCCL培养基在SCCL的原发性培养物中起源于汽车患者，（b）研究实验动物对敏化对敏化的免疫学反应潜在的葡萄膜源性视网膜抗原和特异性肽分子的成分和（c）表征了基因的性质表达视网膜抗原和相应的抗原在肺的小细胞癌中鉴定出的成分。该研究将结合免疫学和分子生物学确定视网膜超敏反应的指征的技术与汽车相关的是免疫介导的视力丧失的例子由抗原交叉反应产生。