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Improved retinal function in RCS rats after suppressing the over-activation of mGluR5

Müller cells maintain retinal synaptic homeostasis by taking up glutamate from the synaptic cleft and transporting glutamine back to the neurons. To study the interaction between Müller cells and photoreceptors, we injected either DL-α-aminoadipate or L-methionine sulfoximine–both inhibitors of glut...

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Autores principales: Dai, Jiaman, Fu, Yan, Zeng, Yuxiao, Li, Shiying, Qin Yin, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471183/
https://www.ncbi.nlm.nih.gov/pubmed/28615682
http://dx.doi.org/10.1038/s41598-017-03702-z
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author Dai, Jiaman
Fu, Yan
Zeng, Yuxiao
Li, Shiying
Qin Yin, Zheng
author_facet Dai, Jiaman
Fu, Yan
Zeng, Yuxiao
Li, Shiying
Qin Yin, Zheng
author_sort Dai, Jiaman
collection PubMed
description Müller cells maintain retinal synaptic homeostasis by taking up glutamate from the synaptic cleft and transporting glutamine back to the neurons. To study the interaction between Müller cells and photoreceptors, we injected either DL-α-aminoadipate or L-methionine sulfoximine–both inhibitors of glutamine synthetase–subretinally in rats. Following injection, the a-wave of the electroretinogram (ERG) was attenuated, and metabotropic glutamate receptor 5 (mGluR5) was activated. Selective antagonism of mGluR5 by 2-methyl-6-(phenylethynyl)-pyridine increased the ERG a-wave amplitude and also increased rhodopsin expression. Conversely, activation of mGluR5 by the agonist, (R,S)-2-chloro-5-hydroxyphenylglycine, decreased both the a-wave amplitude and rhodopsin expression, but upregulated expression of G(q) alpha subunit and phospholipase C βIII. Overexpression of mGluR5 reduced the inward-rectifying potassium ion channel (K(ir)) current and decreased the expression of K(ir)4.1 and aquaporin-4 (AQP4). Further experiments indicated that mGluR5 formed a macromolecular complex with these two membrane channels. Lastly, increased expression of mGluR5 was found in Royal College of Surgeons rats–a model of retinitis pigmentosa (RP). Inhibition of mGluR5 in this model restored the amplitude of ERG features, and reduced the expression of glial fibrillary acidic protein. These results suggest that mGluR5 may be worth considering as a potential therapeutic target in RP.
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spelling pubmed-54711832017-06-19 Improved retinal function in RCS rats after suppressing the over-activation of mGluR5 Dai, Jiaman Fu, Yan Zeng, Yuxiao Li, Shiying Qin Yin, Zheng Sci Rep Article Müller cells maintain retinal synaptic homeostasis by taking up glutamate from the synaptic cleft and transporting glutamine back to the neurons. To study the interaction between Müller cells and photoreceptors, we injected either DL-α-aminoadipate or L-methionine sulfoximine–both inhibitors of glutamine synthetase–subretinally in rats. Following injection, the a-wave of the electroretinogram (ERG) was attenuated, and metabotropic glutamate receptor 5 (mGluR5) was activated. Selective antagonism of mGluR5 by 2-methyl-6-(phenylethynyl)-pyridine increased the ERG a-wave amplitude and also increased rhodopsin expression. Conversely, activation of mGluR5 by the agonist, (R,S)-2-chloro-5-hydroxyphenylglycine, decreased both the a-wave amplitude and rhodopsin expression, but upregulated expression of G(q) alpha subunit and phospholipase C βIII. Overexpression of mGluR5 reduced the inward-rectifying potassium ion channel (K(ir)) current and decreased the expression of K(ir)4.1 and aquaporin-4 (AQP4). Further experiments indicated that mGluR5 formed a macromolecular complex with these two membrane channels. Lastly, increased expression of mGluR5 was found in Royal College of Surgeons rats–a model of retinitis pigmentosa (RP). Inhibition of mGluR5 in this model restored the amplitude of ERG features, and reduced the expression of glial fibrillary acidic protein. These results suggest that mGluR5 may be worth considering as a potential therapeutic target in RP. Nature Publishing Group UK 2017-06-14 /pmc/articles/PMC5471183/ /pubmed/28615682 http://dx.doi.org/10.1038/s41598-017-03702-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Dai, Jiaman
Fu, Yan
Zeng, Yuxiao
Li, Shiying
Qin Yin, Zheng
Improved retinal function in RCS rats after suppressing the over-activation of mGluR5
title Improved retinal function in RCS rats after suppressing the over-activation of mGluR5
title_full Improved retinal function in RCS rats after suppressing the over-activation of mGluR5
title_fullStr Improved retinal function in RCS rats after suppressing the over-activation of mGluR5
title_full_unstemmed Improved retinal function in RCS rats after suppressing the over-activation of mGluR5
title_short Improved retinal function in RCS rats after suppressing the over-activation of mGluR5
title_sort improved retinal function in rcs rats after suppressing the over-activation of mglur5
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471183/
https://www.ncbi.nlm.nih.gov/pubmed/28615682
http://dx.doi.org/10.1038/s41598-017-03702-z
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