Format

Send to

Choose Destination
Sci Rep. 2017 Jun 14;7(1):3546. doi: 10.1038/s41598-017-03702-z.

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

Dai J1,2, Fu Y3,2, Zeng Y3,2, Li S4,5, Qin Yin Z6,7,8.

Author information

1
Bioengineering College, Chongqing University, Chongqing, 400040, China.
2
Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China.
3
Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.
4
Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China. shiying_li@126.com.
5
Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China. shiying_li@126.com.
6
Bioengineering College, Chongqing University, Chongqing, 400040, China. qinzyin@aliyun.com.
7
Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China. qinzyin@aliyun.com.
8
Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China. qinzyin@aliyun.com.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center