Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
PLoS One. 2011;6(5):e19911. doi: 10.1371/journal.pone.0019911. Epub 2011 May 17.
Paraneoplastic retinopathy (PR), including cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), is a progressive retinal disease caused by antibodies generated against neoplasms not associated with the eye. While several autoantibodies against retinal antigens have been identified, there has been no known autoantibody reacting specifically against bipolar cell antigens in the sera of patients with PR. We previously reported that the transient receptor potential cation channel, subfamily M, member 1 (TRPM1) is specifically expressed in retinal ON bipolar cells and functions as a component of ON bipolar cell transduction channels. In addition, this and other groups have reported that human TRPM1 mutations are associated with the complete form of congenital stationary night blindness. The purpose of the current study is to investigate whether there are autoantibodies against TRPM1 in the sera of PR patients exhibiting ON bipolar cell dysfunction.
METHODOLOGY/PRINCIPAL FINDINGS: We performed Western blot analysis to identify an autoantibody against TRPM1 in the serum of a patient with lung CAR. The electroretinograms of this patient showed a severely reduced ON response with normal OFF response, indicating that the defect is in the signal transmission between photoreceptors and ON bipolar cells. We also investigated the sera of 26 patients with MAR for autoantibodies against TRPM1 because MAR patients are known to exhibit retinal ON bipolar cell dysfunction. Two of the patients were found to have autoantibodies against TRPM1 in their sera.
CONCLUSION/SIGNIFICANCE: Our study reveals TRPM1 to be one of the autoantigens targeted by autoantibodies in at least some patients with CAR or MAR associated with retinal ON bipolar cell dysfunction.
副肿瘤性视网膜病变（PR），包括癌症相关视网膜病变（CAR）和黑色素瘤相关视网膜病变（MAR），是一种由针对与眼无关的肿瘤产生的抗体引起的进行性视网膜疾病。虽然已经鉴定出几种针对视网膜抗原的自身抗体，但尚未发现针对 PR 患者血清中双极细胞抗原的特异性自身抗体。我们之前报道过，瞬时受体电位阳离子通道，亚家族 M，成员 1（TRPM1）特异性表达在视网膜 ON 双极细胞中，并作为 ON 双极细胞转导通道的组成部分发挥作用。此外，该和其他组报道称，人类 TRPM1 突变与先天性静止性夜盲的完全形式有关。本研究的目的是研究在表现出 ON 双极细胞功能障碍的 PR 患者的血清中是否存在针对 TRPM1 的自身抗体。
方法/主要发现：我们进行了 Western blot 分析，以鉴定一位患有 CAR 的患者血清中针对 TRPM1 的自身抗体。该患者的视网膜电图显示 ON 反应严重降低，而 OFF 反应正常，表明缺陷存在于光感受器和 ON 双极细胞之间的信号传递中。我们还研究了 26 名 MAR 患者的血清中针对 TRPM1 的自身抗体，因为已知 MAR 患者表现出视网膜 ON 双极细胞功能障碍。发现其中两名患者的血清中存在针对 TRPM1 的自身抗体。
结论/意义：我们的研究揭示了 TRPM1 是至少一些与视网膜 ON 双极细胞功能障碍相关的 CAR 或 MAR 患者自身抗体靶向的自身抗原之一。
