关键词: MAR Melanoma TRPM1 autoantibodies autoimmune retinopathy bipolar cells paraneoplastic syndrome retina

来  源:   DOI:10.21203/rs.3.rs-4595829/v1   PDF(Pubmed)

Abstract:
Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with cutaneous metastatic melanoma in which patients develop vision deficits that include reduced night vision, poor contrast sensitivity, and photopsia. MAR is caused by autoantibodies targeting TRPM1, an ion channel found in melanocytes and retinal ON-bipolar cells (ON-BCs). The visual symptoms arise when TRPM1 autoantibodies enter ON-BCs and block the function of TRPM1, thus detection of TRPM1 autoantibodies in patient serum is a key criterion in diagnosing MAR. Electroretinograms are used to measure the impact of TRPM1 autoantibodies on ON-BC function and represent another important diagnostic tool for MAR. To date, MAR case reports have included one or both diagnostic components, but only for a single time point in the course of a patient\'s disease. Here, we report a case of MAR supported by longitudinal analysis of serum autoantibody detection, visual function, ocular inflammation, vascular integrity, and response to slow-release intraocular corticosteroids. Integrating these data with the patient\'s oncological and ophthalmological records reveals novel insights regarding MAR pathogenesis, progression, and treatment, which may inform new research and expand our collective understanding of the disease. In brief, we find TRPM1 autoantibodies can disrupt vision even when serum levels are barely detectable by western blot and immunohistochemistry; intraocular dexamethasone treatment alleviates MAR visual symptoms despite high levels of circulating TRPM1 autoantibodies, implicating antibody access to the retina as a key factor in MAR pathogenesis. Elevated inflammatory cytokine levels in the patient\'s eyes may be responsible for the observed damage to the blood-retinal barrier and subsequent entry of autoantibodies into the retina.
摘要:
黑色素瘤相关视网膜病变(MAR)是一种与皮肤转移性黑色素瘤相关的副肿瘤综合征,患者出现视力缺陷,包括夜视功能下降,对比敏感度差,和光视。MAR是由靶向TRPM1的自身抗体引起的,TRPM1是在黑素细胞和视网膜ON双极细胞(ON-BC)中发现的离子通道。当TRPM1自身抗体进入ON-BCs并阻断TRPM1的功能时出现视觉症状,因此在患者血清中检测TRPM1自身抗体是诊断MAR的关键标准。视网膜电图用于测量TRPM1自身抗体对ON-BC功能的影响,并代表MAR的另一个重要诊断工具。迄今为止,MAR病例报告包括一个或两个诊断组件,但只针对患者疾病过程中的单个时间点。这里,我们报告了一例由血清自身抗体检测的纵向分析支持的MAR,视觉功能,眼部炎症,血管完整性,以及对缓释眼内皮质类固醇的反应。将这些数据与患者的肿瘤和眼科记录相结合,揭示了有关MAR发病机制的新见解。programming,和治疗,这可能为新的研究提供信息,扩大我们对这种疾病的集体理解。简而言之,我们发现TRPM1自身抗体即使在westernblot和免疫组织化学几乎检测不到血清水平时也能破坏视力;尽管循环中的TRPM1自身抗体水平很高,但眼内地塞米松治疗可缓解MAR视觉症状,提示抗体进入视网膜是MAR发病机制的关键因素。患者眼睛中炎性细胞因子水平升高可能是观察到的血-视网膜屏障损伤以及随后自身抗体进入视网膜的原因。
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