Mosavi-Hecht Ryan, Yang Paul, Heyer Barrett, Rosenberg Christopher R, White Elizabeth, Berry Elizabeth G, Duvoisin Robert M, Morgans Catherine W
Oregon Health and Science University.
Oregon Health and Science University, Casey Eye Institute.
Res Sq. 2024 Jun 19:rs.3.rs-4595829. doi: 10.21203/rs.3.rs-4595829/v1.
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.
黑色素瘤相关性视网膜病变（MAR）是一种与皮肤转移性黑色素瘤相关的副肿瘤综合征，患者会出现视力缺陷，包括夜视能力下降、对比敏感度降低和闪光感。MAR由靶向TRPM1的自身抗体引起，TRPM1是一种在黑素细胞和视网膜ON双极细胞（ON-BCs）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，就会出现视觉症状，因此检测患者血清中的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，是MAR的另一种重要诊断工具。迄今为止，MAR病例报告仅包含其中一项或两项诊断指标，且仅针对患者病程中的单个时间点。在此，我们报告一例通过对血清自身抗体检测、视觉功能、眼部炎症、血管完整性以及缓释眼内糖皮质激素反应进行纵向分析来支持的MAR病例。将这些数据与患者的肿瘤学和眼科记录相结合，揭示了关于MAR发病机制、进展和治疗的新见解，这可能为新的研究提供信息，并扩展我们对该疾病的总体认识。简而言之，我们发现即使通过蛋白质印迹法和免疫组织化学法几乎检测不到血清水平，TRPM1自身抗体也会破坏视力；眼内注射地塞米松治疗可缓解MAR的视觉症状，尽管循环中的TRPM1自身抗体水平很高，这表明抗体进入视网膜是MAR发病机制中的一个关键因素。患者眼中炎症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。
