Effects of autoantibodies on synaptic transmission in the retina

自身抗体对视网膜突触传递的影响

基本信息

批准号：
8634104
负责人：
CATHERINE W MORGANS
金额：
$ 46.24万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8634104
关键词：
Address Agonist Antibodies Antigens Appearance Autoantibodies Autoimmune Process Binding Biochemistry Cations Cell physiology Cells Cellular biology Clinic Complex Confocal Microscopy Cutaneous Melanoma Data Defect Diagnosis Disease Early Diagnosis Electrophysiology (science)Electroretinography Epitopes Esthesia Eye Family Goals Heterotrimeric GTP-Binding Proteins Immune response Immunization Immunofluorescence Microscopy Immunoglobulin G Immunohistochemistry Immunotherapy Knock-out Knockout Mice Label Life Light Link Malignant - descriptor Malignant Neoplasms Measures Mediating Mus Neoplasm Metastasis Night Blindness Patients Phenotype Photoreceptors Physiological Protein Isoforms Protein Region Proteins RGS Proteins Recombinant Proteins Recombinants Reporting Research Retina Retinal Retinal Diseases Retinal Photoreceptors Role Serum Signal Transduction Structure of retinal pigment epithelium Symptoms Synaptic Transmission Syndrome Testing Vision Visual Western Blotting XLRS1 protein cancer risk cell type cross reactivity design experience follow-up ganglion cell immunogenic immunoreactivity insight interdisciplinary approach melanocyte melanoma member mouse model polypeptide protein complex public health relevance response screening transmission process treatment strategy tumor uptake visual process visual processing

项目摘要

DESCRIPTION (provided by applicant): Melanoma Associated Retinopathy (MAR) is a paraneoplastic visual syndrome associated with cutaneous malignant melanoma in which patients typically experience a sudden decrease in night vision and sensations of shimmering lights. Electroretinogram (ERG) recordings from MAR patients are characterized by a "negative" waveform in which the a-wave, arising from photoreceptor transduction, is normal, but the b-wave, arising primarily from ON-bipolar cell activation, is absent or reduced. Significantly, serum from MAR patients has been shown to label retinal bipolar cells. The proposed research tests the hypothesis that autoantibodies in MAR patient serum are generated against proteins expressed in metastatic malignant melanocytes, but then target a protein complex functional in bipolar cells. The aims of the research are to identify the retinal antigens in MAR, to elucidate the role of these proteins in normal bipolar cell physiology, and determine how these functions are perturbed in MAR. The aims will be addressed with a multidisciplinary approach combining immunohistochemistry, cell biology, biochemistry, and electrophysiology. The results will generate new insights into cellular processes fundamental to vision and will contribute to our understanding of the link between cancer and autoimmune retinopathy.

描述（由申请人提供）：黑色素瘤相关视网膜病（MAR）是一种与皮肤恶性黑色素瘤相关的副肿瘤性视觉综合征，患者通常会经历夜视力突然下降和闪烁灯光的感觉。 MAR 患者的视网膜电图 (ERG) 记录的特点是“负”波形，其中由光感受器转导产生的 a 波正常，但主要由 ON-双极细胞激活产生的 b 波缺失或减少。值得注意的是，血清来自 MAR 患者的细胞已被证明可以标记视网膜双极细胞。拟议的研究测试了这样的假设：MAR 患者血清中的自身抗体是针对转移性恶性黑素细胞中表达的蛋白质产生的，然后针对双极细胞中功能性的蛋白质复合物。该研究的目的是鉴定 MAR 中的视网膜抗原，阐明这些蛋白质在正常双极细胞生理学中的作用，并确定这些功能在 MAR 中如何受到干扰。这些目标将通过结合免疫组织化学、细胞生物学、生物化学和电生理学的多学科方法来实现。这些结果将对视觉基础细胞过程产生新的见解，并将有助于我们理解癌症和自身免疫性视网膜病变之间的联系。