April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Identification Of Autoantibodies Against Trpm1 In Patients With Paraneoplastic Retinopathy Associated With On Bipolar Cell Dysfunction
Author Affiliations & Notes
  • Mineo Kondo
    Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Rikako Sanuki
    Developmental Biology, Osaka Bioscience Institute, Osaka, Japan
    JST, CREST, Osaka, Japan
  • Shinji Ueno
    Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Yuji Nishizawa
    Biomedical Sciences, Chubu University, Kasugai, Japan
  • Hiroshi Ohguro
    Ophthalmology, Sapporo Medical University School of Medicine, Sapporo, Japan
  • Shuichi Yamamoto
    Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan
  • Shigeki Machida
    Ophthalmology, Iwate Medical University School of Medicine, Morioka, Japan
  • Hiroko Terasaki
    Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Grazyna Adamus
    Ophthal-Casey Eye Inst, Oregon Health Sciences University, Portland, Oregon
  • Takahisa Furukawa
    Developmental Biology, Osaka Bioscience Institute, Osaka, Japan
    JST, CREST, Osaka, Japan
  • Footnotes
    Commercial Relationships  Mineo Kondo, None; Rikako Sanuki, None; Shinji Ueno, None; Yuji Nishizawa, None; Hiroshi Ohguro, None; Shuichi Yamamoto, None; Shigeki Machida, None; Hiroko Terasaki, None; Grazyna Adamus, None; Takahisa Furukawa, None
  • Footnotes
    Support  This work was supported by CREST from Japan Science and Technology Agency (http://www.jst.go.jp/), and a Grant-in-Aid for Scientific Research (B)(C) (#20390448, #20390087, #20592075, #20791678)
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 6667. doi:
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      Mineo Kondo, Rikako Sanuki, Shinji Ueno, Yuji Nishizawa, Hiroshi Ohguro, Shuichi Yamamoto, Shigeki Machida, Hiroko Terasaki, Grazyna Adamus, Takahisa Furukawa; Identification Of Autoantibodies Against Trpm1 In Patients With Paraneoplastic Retinopathy Associated With On Bipolar Cell Dysfunction. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6667.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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, we 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 is an autoantibody against TRPM1 in the sera of patients with paraneoplastic retinopathy (PR) exhibiting ON bipolar cell dysfunction.

Methods: : Of the PR patients that were examined in the Nagoya University Hospital, one PR patient with lung cancer and ON bipolar cell dysfunction was studied in detail. The examinations included routine ophthalmological and electrophysiological tests. Inaddition, immunohistochemical and Western blot analyses were performed using the serum of this patient. The sera of 26 patients with melanoma-associated retinopathy (MAR) were also studied with Western blot analysis.

Results: : We identified an autoantibody against TRPM1 in the serum of a patient with lung cancer-associated retinopathy (CAR) using Western blot analysis. 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 an autoantibody 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 the sera.

Conclusions: : Our study reveals TRPM1 to be an autoantigen targeted by autoantibodies in PR associated with retinal ON bipolar cell dysfunction and leads to a better understanding of PR pathogenesis.

Keywords: CAR • bipolar cells • melanoma 
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