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

Abstract 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 inhibitor...

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Autores principales:	Jiaman Dai, Yan Fu, Yuxiao Zeng, Shiying Li, Zheng Qin Yin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0dc008a5db864625a72eccf0b33fa047
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spelling	oai:doaj.org-article:0dc008a5db864625a72eccf0b33fa0472021-12-02T15:18:53ZImproved retinal function in RCS rats after suppressing the over-activation of mGluR510.1038/s41598-017-03702-z2045-2322https://doaj.org/article/0dc008a5db864625a72eccf0b33fa0472017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03702-zhttps://doaj.org/toc/2045-2322Abstract 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 Gq alpha subunit and phospholipase C βIII. Overexpression of mGluR5 reduced the inward-rectifying potassium ion channel (Kir) current and decreased the expression of Kir4.1 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.Jiaman DaiYan FuYuxiao ZengShiying LiZheng Qin YinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiaman Dai Yan Fu Yuxiao Zeng Shiying Li Zheng Qin Yin Improved retinal function in RCS rats after suppressing the over-activation of mGluR5
description	Abstract 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 Gq alpha subunit and phospholipase C βIII. Overexpression of mGluR5 reduced the inward-rectifying potassium ion channel (Kir) current and decreased the expression of Kir4.1 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.
format	article
author	Jiaman Dai Yan Fu Yuxiao Zeng Shiying Li Zheng Qin Yin
author_facet	Jiaman Dai Yan Fu Yuxiao Zeng Shiying Li Zheng Qin Yin
author_sort	Jiaman Dai
title	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_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_sort	improved retinal function in rcs rats after suppressing the over-activation of mglur5
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0dc008a5db864625a72eccf0b33fa047
work_keys_str_mv	AT jiamandai improvedretinalfunctioninrcsratsaftersuppressingtheoveractivationofmglur5 AT yanfu improvedretinalfunctioninrcsratsaftersuppressingtheoveractivationofmglur5 AT yuxiaozeng improvedretinalfunctioninrcsratsaftersuppressingtheoveractivationofmglur5 AT shiyingli improvedretinalfunctioninrcsratsaftersuppressingtheoveractivationofmglur5 AT zhengqinyin improvedretinalfunctioninrcsratsaftersuppressingtheoveractivationofmglur5
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Improved retinal function in RCS rats after suppressing the over-activation of mGluR5

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