MECHANISM OF RETINAL DAMAGE IN AUTOIMMUNE RETINOPATHY

自身免疫性视网膜病视网膜损伤的机制

• 批准号: 8173221
• 负责人: Brett G Jeffrey
• 金额: $ 4.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173221
• 关键词: Accounting; Antibodies; Autoantibodies; Autoimmune Process; Blindness; Body part; Computer Retrieval of Information on Scientific Projects Database; Cornea; Disease; Distal; Electrodes; Electroretinography; Epitopes; Functional disorder; Funding; Grant; Immune response; Injection of therapeutic agent; Institution; Lead; Light; Malignant Neoplasms; Molecular; Patients; Prevention; Proteins; Rattus; Research; Research Personnel; Resources; Retina; Retinal; Retinal Degeneration; Retinal Diseases; Serum; Source; Testing; United States National Institutes of Health; Variant; carbonate dehydratase; enolase; recoverin protein; response; retinal damage; voltage

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cancer Associated Retinopathy (CAR) is a paraneoplastic disease in which retinal degeneration occurs as a result of the patient's immune response to cancer in a distal part of the body. Treatment for the primary malignancy does not alter the course of visual loss and there is neither a means of cure nor prevention of such retinal degenerations. Autoantibodies against retinal proteins are present in serum of CAR patients but whether these antibodies themselves induce retinal degeneration is a source of debate. Retinal dysfunction or degeneration is assessed by recording the electroretinogram (ERG). The ERG is a recording of the change in voltage across the retina in response to light and is recorded from an electrode placed against the cornea. The aim of the proposed studies was to use the ERG to assess changes in retinal function in rats following intravitreal injection autoantibodies isolated from CAR patients. The overall aim of the research is to determine the molecular mechanisms altered by autoantibodies against retinal proteins that lead to retinal degeneration. Understanding the molecular mechanisms that result in retinal degeneration in these patients is the first step towards the developing and testing of preventative treatments. Retinal function was not altered following intra-vitreal injection of antibodies against recoverin, alpha-enolase or carbonic anhydrase. Why these antibodies obtained from CAR patients did no alter the ERG remains unknown. Variation in epitope recognition, for example, between our patients may account for some of the variability in ERG results, and in patients. Another possibility is that a single injection of autoantibodies does not mimic the continuous exposure of the retina to these antibodies as occurs in CAR patients.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 癌症相关性视网膜病变（CAR）是一种副肿瘤疾病，其中视网膜变性是由于患者对身体远端部分的癌症的免疫应答而发生的。原发性恶性肿瘤的治疗不会改变视力丧失的过程，并且既没有治愈也没有预防这种视网膜变性的方法。针对视网膜蛋白的自身抗体存在于CAR患者的血清中，但这些抗体本身是否诱导视网膜变性是一个争论的来源。通过记录视网膜电图（ERG）来评估视网膜功能障碍或变性。ERG是对视网膜上响应于光的电压变化的记录，并且从抵靠角膜放置的电极记录。拟议研究的目的是使用ERG评估玻璃体内注射从CAR患者分离的自身抗体后大鼠视网膜功能的变化。这项研究的总体目标是确定针对视网膜蛋白的自身抗体改变导致视网膜变性的分子机制。了解导致这些患者视网膜变性的分子机制是开发和测试预防性治疗的第一步。 视网膜功能没有改变后，玻璃体内注射的抗体对recoverin，α-烯醇化酶或碳酸酐酶。为什么从CAR患者中获得的这些抗体没有改变ERG仍然是未知的。例如，我们的患者之间表位识别的变化可能是ERG结果和患者中的一些变异性的原因。另一种可能性是，单次注射自身抗体不会模拟视网膜连续暴露于CAR患者中发生的这些抗体。