Effects of autoantibodies on synaptic transmission in the retina

自身抗体对视网膜突触传递的影响

• 批准号: 8504164
• 负责人: CATHERINE W MORGANS
• 金额: $ 47.19万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 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/8504164
• 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

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）：黑色素瘤相关的视网膜病（MAR）是一种与皮肤恶性黑色素瘤相关的副塑性视觉综合征，其中患者通常会突然降低夜视和闪烁灯光的感觉。来自MAR患者的电视图（ERG）记录的特征是“负”波形，其中由光感受器转导引起的A波是正常的，但是主要由双极细胞激活引起的B波是不存在或减少的。重要的是，血清 来自MAR患者已显示出标记视网膜双极细胞。拟议的研究检验了以下假设：MAR患者血清中的自身抗体是针对转移性恶性黑色素细胞中表达的蛋白质产生的，但随后靶向在双极细胞中的蛋白质复合物。该研究的目的是鉴定MAR中的视网膜抗原，以阐明这些蛋白质在正常的双极细胞生理学中的作用，并确定这些功能在MAR中的干扰。该目标将采用多学科方法来解决，该方法结合了免疫组织化学，细胞生物学，生物化学和电生理学。结果将产生对视觉基础的细胞过程的新见解，并将有助于我们理解癌症与自身免疫性视网膜病之间的联系。