文章基本信息

标题：Improved retinal function in RCS rats after suppressing the over-activation of mGluR5
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作者：Jiaman Dai ; Yan Fu ; Yuxiao Zeng 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/s41598-017-03702-z
语种：English
出版社：Springer Nature
摘要：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.