Identification of Autoantibodies against TRPM1 in Patients with Paraneoplastic Retinopathy Associated with ON Bipolar Cell Dysfunction

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

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.

Related collections

Most cited references 31

Record: found
Abstract: found
Article: not found

Autoimmune retinopathy: a review and summary.

Gustavo Ferreyra, John R. Heckenlively (2008)

Three main forms of autoimmune retinopathy (AIR) have been identified over the last 15 years: cancer-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), and nonneoplastic autoimmune retinopathy (npAIR). In this chapter, the term AIR will be used to encompass all three disorders where there is commonality to their features. Complicating the issue is that AIR can be a secondary complication of other conditions such as retinitis pigmentosa, ocular trauma, birdshot retinopathy, acute zonal occult outer retinopathy (AZOOR), or multiple evanescent white dot syndrome (MEWDS). The many forms of AIR tend to have common clinical features despite the fact that there has been no uniform set of anti-retinal antibodies circulating in these patients. Patients tend to have a wide variance of anti-retinal antibody activity often with three to six different antibodies found on immunoblots. Patients typically present with a sudden onset of photopsia, rapid visual loss, and abnormal electroretinograms (ERGs). Most patients have a panretinal degeneration without pigment deposits.

0 comments Cited 69 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness.

Jesper N Bech, R Weleber, R Sparkes … (2000)

During development, visual photoreceptors, bipolar cells and other neurons establish connections within the retina enabling the eye to process visual images over approximately 7 log units of illumination. Within the retina, cells that respond to light increment and light decrement are separated into ON- and OFF-pathways. Hereditary diseases are known to disturb these retinal pathways, causing either progressive degeneration or stationary deficits. Congenital stationary night blindness (CSNB) is a group of stable retinal disorders that are characterized by abnormal night vision. Genetic subtypes of CSNB have been defined and different disease actions have been postulated. The molecular bases have been elucidated in several subtypes, providing a better understanding of the disease mechanisms and developmental retinal neurobiology. Here we have studied 22 families with 'complete' X-linked CSNB (CSNB1; MIM 310500; ref. 4) in which affected males have night blindness, some photopic vision loss and a defect of the ON-pathway. We have found 14 different mutations, including 1 founder mutation in 7 families from the United States, in a novel candidate gene, NYX. NYX, which encodes a glycosylphosphatidyl (GPI)-anchored protein called nyctalopin, is a new and unique member of the small leucine-rich proteoglycan (SLRP) family. The role of other SLRP proteins suggests that mutant nyctalopin disrupts developing retinal interconnections involving the ON-bipolar cells, leading to the visual losses seen in patients with complete CSNB.

0 comments Cited 69 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6.

M Sandberg, G Fishman, S. Rajagopalan … (2005)

We report three unrelated patients with mutations in the GRM6 gene that normally encodes the glutamate receptor mGluR6. This neurotransmitter receptor has been shown previously to be present only in the synapses of the ON bipolar cell dendrites, and it mediates synaptic transmission from rod and cone photoreceptors to this type of second-order neuron. Despite the synaptic defect, best visual acuities were normal or only moderately reduced (20/15 to 20/40). The patients were night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system (i.e., 2-3 log units above normal). Electroretinograms (ERGs) in response to single brief flashes of light had clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicated a markedly reduced ON response and a nearly normal OFF response. There was no subjective delay in the perception of suddenly appearing white vs. black objects on a gray background. These patients exemplify a previously unrecognized, autosomal recessive form of congenital night blindness associated with a negative ERG waveform.

0 comments Cited 66 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2011

Publication date (Electronic): 17 May 2011

Volume: 6

Issue: 5

Electronic Location Identifier: e19911

Affiliations

[1 ]Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan

[2 ]Department of Developmental Biology, Osaka Bioscience Institute, Suita, Osaka, Japan

[3 ]JST, CREST, Suita, Osaka, Japan

[4 ]Department of Biomedical Sciences, Chubu University, Kasugai, Aichi, Japan

[5 ]Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan

[6 ]Department of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan

[7 ]Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan

[8 ]Department of Ophthalmology, Iwate Medical University School of Medicine, Morioka, Iwate, Japan

[9 ]Department of Ophthalmology, Oregon Health and Science University, Portland, Oregon, United States of America

Dalhousie University, Canada

Author notes

* E-mail: furukawa@ 123456obi.or.jp (TF); kondomi@ 123456med.nagoya-u.ac.jp (MK)

Conceived and designed the experiments: MK TF. Performed the experiments: MK RS SU YN NH. Analyzed the data: MK RS SU TF. Contributed reagents/materials/analysis tools: MK SU HO SY SM HT GA. Wrote the paper: MK TF. Supervised the project: MK HT TF.

Article

Publisher ID: PONE-D-11-03057

DOI: 10.1371/journal.pone.0019911

PMC ID: 3096646

PubMed ID: 21611200

SO-VID: 63c22b06-5b1a-4834-bb6e-174b4f3fc799

Copyright © Kondo et al. 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 credited.

History

Date received : 10 February 2011

Date accepted : 6 April 2011

Page count

Pages: 7

Comments

Comment on this article

scite_

Cited by 26

See all cited by

Most referenced authors 273

See all reference authors

Identification of Autoantibodies against TRPM1 in Patients with Paraneoplastic Retinopathy Associated with ON Bipolar Cell Dysfunction

Read this article at

Abstract

Background

Methodology/Principal Findings

Conclusion/Significance

Related collections

PLOS Climate

Most cited references 31

Autoimmune retinopathy: a review and summary.

Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness.

Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 719

Cited by 26

Most referenced authors 273