title: Identification of autoantibodies against TRPM1 in patients with paraneoplastic retinopathy associated with ON bipolar cell dysfunction.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. kondomi@med.nagoya-u.ac.jp
authors: Mineo
authors: M
authors: Kondo
authors: Rikako
authors: R
authors: Sanuki
authors: Shinji
authors: S
authors: Ueno
authors: Yuji
authors: Y
authors: Nishizawa
authors: Naozumi
authors: N
authors: Hashimoto
authors: Hiroshi
authors: H
authors: Ohguro
authors: Shuichi
authors: S
authors: Yamamoto
authors: Shigeki
authors: S
authors: Machida
authors: Hiroko
authors: H
authors: Terasaki
authors: Grazyna
authors: G
authors: Adamus
authors: Takahisa
authors: T
authors: Furukawa
references: Br J Cancer. 1996 Nov;74(9):1419-22
references: 8912538
references: Am J Hum Genet. 2009 Nov;85(5):730-6
references: 19896109
references: Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4884-9
references: 15781871
references: Am J Hum Genet. 2009 Nov;85(5):711-9
references: 19878917
references: Am J Ophthalmol. 2001 Jun;131(6):806-8
references: 11384586
references: Am J Hum Genet. 2009 Nov;85(5):720-9
references: 19896113
references: Surv Ophthalmol. 2003 Jan-Feb;48(1):12-38
references: 12559325
references: Invest Ophthalmol Vis Sci. 2000 Jan;41(1):262-6
references: 10634629
references: Nat Genet. 2000 Nov;26(3):324-7
references: 11062472
references: Jpn J Ophthalmol. 1987;31(1):81-7
references: 3498069
references: Int J Cancer. 2005 Mar 10;114(1):88-93
references: 15523688
references: Int J Cancer. 2007 Mar 15;120(6):1268-76
references: 17187367
references: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):332-7
references: 19966281
references: Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19174-8
references: 19861548
references: Semin Immunopathol. 2008 Apr;30(2):127-34
references: 18408929
references: Arch Ophthalmol. 1987 Mar;105(3):372-5
references: 2950846
references: Cell Calcium. 2010 Aug-Sep;48(2-3):95-101
references: 20846719
references: Tohoku J Exp Med. 2004 Mar;202(3):213-9
references: 15065647
references: Am J Ophthalmol. 2002 Jul;134(1):128-30
references: 12095824
references: Nat Genet. 2000 Nov;26(3):319-23
references: 11062471
references: Autoimmun Rev. 2009 Mar;8(5):410-4
references: 19168157
references: Ann Neurol. 1990 Aug;28(2):162-7
references: 2171418
references: J Neurophysiol. 2005 Jan;93(1):481-92
references: 15331616
references: J Neuroophthalmol. 2008 Mar;28(1):5-11
references: 18347451
references: Mol Vis. 2010 Mar 12;16:425-37
references: 20300565
references: Invest Ophthalmol Vis Sci. 1993 Jan;34(1):91-100
references: 8425845
references: Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9176-80
references: 7568096
references: Invest Ophthalmol Vis Sci. 1992 Mar;33(3):477-83
references: 1544774
references: Doc Ophthalmol. 2008 Jan;116(1):49-55
references: 17721792
references: Arch Ophthalmol. 1986 Jul;104(7):1013-20
references: 3488053
references: N Engl J Med. 1989 Dec 7;321(23):1589-94
references: 2555714
references: Arch Ophthalmol. 2009 Dec;127(12):1572-80
references: 20008709
references: J Neuroophthalmol. 1999 Jun;19(2):71-83
references: 10380127