Degeneration of Retinal ON Bipolar Cells Induced by Serum Including Autoantibody against TRPM1 in Mouse Model of Paraneoplastic Retinopathy

The paraneoplastic retinopathies (PRs) are a group of eye diseases characterized by a sudden and progressive dysfunction of the retina caused by an antibody against a protein in a neoplasm. Evidence has been obtained that the transient receptor potential melastatin 1 (TRPM1) protein was one of the a...

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Main Authors:	Ueno, Shinji, Nishiguchi, Koji M., Tanioka, Hidetoshi, Enomoto, Atsushi, Yamanouchi, Takashi, Kondo, Mineo, Yasuma, Testuhiro R., Yasuda, Shunsuke, Kuno, Noriyuki, Takahashi, Masahide, Terasaki, Hiroko
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840061/

id	pubmed-3840061
recordtype	oai_dc
spelling	pubmed-38400612013-11-26 Degeneration of Retinal ON Bipolar Cells Induced by Serum Including Autoantibody against TRPM1 in Mouse Model of Paraneoplastic Retinopathy Ueno, Shinji Nishiguchi, Koji M. Tanioka, Hidetoshi Enomoto, Atsushi Yamanouchi, Takashi Kondo, Mineo Yasuma, Testuhiro R. Yasuda, Shunsuke Kuno, Noriyuki Takahashi, Masahide Terasaki, Hiroko Research Article The paraneoplastic retinopathies (PRs) are a group of eye diseases characterized by a sudden and progressive dysfunction of the retina caused by an antibody against a protein in a neoplasm. Evidence has been obtained that the transient receptor potential melastatin 1 (TRPM1) protein was one of the antigens for the autoantibody against the ON bipolar cells in PR patients. However, it has not been determined how the autoantibody causes the dysfunction of the ON bipolar cells. We hypothesized that the antibody against TRPM1 in the serum of patients with PR causes a degeneration of retinal ON bipolar cells. To test this hypothesis, we injected the serum from the PR patient, previously shown to contain anti-TRPM1 antibodies by westerblot, intravitreally into mice and examined the effects on the retina. We found that the electroretinograms (ERGs) of the mice were altered acutely after the injection, and the shape of the ERGs resembled that of the patient with PR. Immunohistochemical analysis of the eyes injected with the serum showed immunoreactivity against bipolar cells only in wild-type animals and not in TRPM1 knockout mice,consistent with the serum containing anti-TRPM1 antibodies. Histology also showed that some of the bipolar cells were apoptotic by 5 hours after the injection in wild type mice, but no bipolar cell death was found in TRPM1 knockout mice, . At 3 months, the inner nuclear layer was thinner and the amplitudes of the ERGs were still reduced. These results indicate that the serum of a patient with PR contained an antibody against TRPM1 caused an acute death of retinal ON bipolar cells of mice. Public Library of Science 2013-11-25 /pmc/articles/PMC3840061/ /pubmed/24282602 http://dx.doi.org/10.1371/journal.pone.0081507 Text en © 2013 Shinji Ueno http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ueno, Shinji Nishiguchi, Koji M. Tanioka, Hidetoshi Enomoto, Atsushi Yamanouchi, Takashi Kondo, Mineo Yasuma, Testuhiro R. Yasuda, Shunsuke Kuno, Noriyuki Takahashi, Masahide Terasaki, Hiroko
spellingShingle	Ueno, Shinji Nishiguchi, Koji M. Tanioka, Hidetoshi Enomoto, Atsushi Yamanouchi, Takashi Kondo, Mineo Yasuma, Testuhiro R. Yasuda, Shunsuke Kuno, Noriyuki Takahashi, Masahide Terasaki, Hiroko Degeneration of Retinal ON Bipolar Cells Induced by Serum Including Autoantibody against TRPM1 in Mouse Model of Paraneoplastic Retinopathy
author_facet	Ueno, Shinji Nishiguchi, Koji M. Tanioka, Hidetoshi Enomoto, Atsushi Yamanouchi, Takashi Kondo, Mineo Yasuma, Testuhiro R. Yasuda, Shunsuke Kuno, Noriyuki Takahashi, Masahide Terasaki, Hiroko
author_sort	Ueno, Shinji
title	Degeneration of Retinal ON Bipolar Cells Induced by Serum Including Autoantibody against TRPM1 in Mouse Model of Paraneoplastic Retinopathy
title_short	Degeneration of Retinal ON Bipolar Cells Induced by Serum Including Autoantibody against TRPM1 in Mouse Model of Paraneoplastic Retinopathy
title_full	Degeneration of Retinal ON Bipolar Cells Induced by Serum Including Autoantibody against TRPM1 in Mouse Model of Paraneoplastic Retinopathy
title_fullStr	Degeneration of Retinal ON Bipolar Cells Induced by Serum Including Autoantibody against TRPM1 in Mouse Model of Paraneoplastic Retinopathy
title_full_unstemmed	Degeneration of Retinal ON Bipolar Cells Induced by Serum Including Autoantibody against TRPM1 in Mouse Model of Paraneoplastic Retinopathy
title_sort	degeneration of retinal on bipolar cells induced by serum including autoantibody against trpm1 in mouse model of paraneoplastic retinopathy
description	The paraneoplastic retinopathies (PRs) are a group of eye diseases characterized by a sudden and progressive dysfunction of the retina caused by an antibody against a protein in a neoplasm. Evidence has been obtained that the transient receptor potential melastatin 1 (TRPM1) protein was one of the antigens for the autoantibody against the ON bipolar cells in PR patients. However, it has not been determined how the autoantibody causes the dysfunction of the ON bipolar cells. We hypothesized that the antibody against TRPM1 in the serum of patients with PR causes a degeneration of retinal ON bipolar cells. To test this hypothesis, we injected the serum from the PR patient, previously shown to contain anti-TRPM1 antibodies by westerblot, intravitreally into mice and examined the effects on the retina. We found that the electroretinograms (ERGs) of the mice were altered acutely after the injection, and the shape of the ERGs resembled that of the patient with PR. Immunohistochemical analysis of the eyes injected with the serum showed immunoreactivity against bipolar cells only in wild-type animals and not in TRPM1 knockout mice,consistent with the serum containing anti-TRPM1 antibodies. Histology also showed that some of the bipolar cells were apoptotic by 5 hours after the injection in wild type mice, but no bipolar cell death was found in TRPM1 knockout mice, . At 3 months, the inner nuclear layer was thinner and the amplitudes of the ERGs were still reduced. These results indicate that the serum of a patient with PR contained an antibody against TRPM1 caused an acute death of retinal ON bipolar cells of mice.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840061/
_version_	1612030479673851904

Degeneration of Retinal ON Bipolar Cells Induced by Serum Including Autoantibody against TRPM1 in Mouse Model of Paraneoplastic Retinopathy

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