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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Autores principales:	Shinji Ueno, Koji M Nishiguchi, Hidetoshi Tanioka, Atsushi Enomoto, Takashi Yamanouchi, Mineo Kondo, Testuhiro R Yasuma, Shunsuke Yasuda, Noriyuki Kuno, Masahide Takahashi, Hiroko Terasaki
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/234216ebaa1f4fba8c618a4143ee964f
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spelling	oai:doaj.org-article:234216ebaa1f4fba8c618a4143ee964f2021-11-18T08:44:47ZDegeneration of retinal on bipolar cells induced by serum including autoantibody against TRPM1 in mouse model of paraneoplastic retinopathy.1932-620310.1371/journal.pone.0081507https://doaj.org/article/234216ebaa1f4fba8c618a4143ee964f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24282602/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Shinji UenoKoji M NishiguchiHidetoshi TaniokaAtsushi EnomotoTakashi YamanouchiMineo KondoTestuhiro R YasumaShunsuke YasudaNoriyuki KunoMasahide TakahashiHiroko TerasakiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e81507 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shinji Ueno Koji M Nishiguchi Hidetoshi Tanioka Atsushi Enomoto Takashi Yamanouchi Mineo Kondo Testuhiro R Yasuma Shunsuke Yasuda Noriyuki Kuno Masahide Takahashi Hiroko Terasaki 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.
format	article
author	Shinji Ueno Koji M Nishiguchi Hidetoshi Tanioka Atsushi Enomoto Takashi Yamanouchi Mineo Kondo Testuhiro R Yasuma Shunsuke Yasuda Noriyuki Kuno Masahide Takahashi Hiroko Terasaki
author_facet	Shinji Ueno Koji M Nishiguchi Hidetoshi Tanioka Atsushi Enomoto Takashi Yamanouchi Mineo Kondo Testuhiro R Yasuma Shunsuke Yasuda Noriyuki Kuno Masahide Takahashi Hiroko Terasaki
author_sort	Shinji Ueno
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.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/234216ebaa1f4fba8c618a4143ee964f
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Degeneration of retinal on bipolar cells induced by serum including autoantibody against TRPM1 in mouse model of paraneoplastic retinopathy.

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