MECHANISM OF RETINAL DAMAGE IN AUTOIMMUNE RETINOPATHY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 癌症相关性视网膜病变(CAR)是一种副肿瘤性疾病，患者对身体远端癌症的免疫反应导致视网膜退化。对原发恶性肿瘤的治疗不会改变视力丧失的进程，也没有治愈或预防这种视网膜退化的方法。抗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会导致视网膜退化仍是一个争论的来源。通过记录视网膜电信号(ERG)来评估视网膜功能障碍或变性。ERG是视网膜上电压对光的反应的记录，是通过放置在角膜上的电极记录的。这项拟议研究的目的是使用ERG来评估玻璃体内注射CAR患者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退化的分子机制是开发和测试预防性治疗的第一步。玻璃体内注射抗恢复素、α-烯醇化酶或碳酸氢酶抗体后，视网膜功能没有改变。为什么从CAR患者身上获得的这些抗体不会改变ERG，目前尚不清楚。例如，我们患者之间表位识别的差异可能解释了ERG结果和患者之间的一些差异。另一种可能性是，单次注射自身抗体并不像CAR患者那样模拟视网膜持续暴露于这些抗体。

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.