Alpha7 nicotinic acetylcholine receptor agonist promotes retinal ganglion cell function via modulating GABAergic presynaptic activity in a chronic glaucomatous model

Scientific Reports
Xujiao ZhouJihong Wu

Abstract

Alpha-7 nicotinic acetylcholine receptor (α7-nAChR) agonists can prevent glutamate-induced excitotoxicity in cultured retinal ganglion cells (RGCs). However, the neuroprotective effects and the mechanism of action of PNU-282987, an α7-nAChR agonist, in a chronic in vivo rat glaucoma model are poorly understood. We found that elevated intraocular pressure (IOP) downregulated retinal α7-nAChR expression. Electroretinography revealed that the amplitude of the photopic negative response (PhNR) decreased in parallel with the loss of RGCs caused by elevated IOP. PNU-282987 enhanced RGC viability and function and decreased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive signals in RGCs. Patch-clamp recordings revealed differences in the baseline frequencies and decay times of the miniature GABAergic inhibitory postsynaptic currents (mIPSCs) of RGCs between control and glaucomatous retinal slices. The results of western blotting and immunostaining showed that glutamic acid decarboxylase 65/67 and GABA deficits persisted in glaucomatous retinas and that these deficits were reversed by PNU-282987. Patch-clamp recordings also showed that PNU-282987 significantly increased the frequency and amplitude of the GA...Continue Reading

References

Sep 1, 1995·Experimental Eye Research·S R ShareefS C Sharma
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Toshiaki KumeAkinori Akaike
Mar 9, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Paulo Roberto LouzadaSérgio T Ferreira
Feb 3, 2005·Cell Research·Tyler Zarubin, Jiahuai Han
Feb 17, 2005·Cell and Tissue Research·Jung-Il MoonMyung-Hoon Chun
May 5, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·María Cecilia MorenoRuth E Rosenstein
May 6, 2005·American Journal of Physiology. Cell Physiology·Christianne E StrangKent T Keyser
May 25, 2005·The Journal of Comparative Neurology·Won-Kyu JuElla Bossy-Wetzel
Jun 28, 2005·Trends in Neurosciences·Rashid GiniatullinJerrel L Yakel
Aug 27, 2005·Investigative Ophthalmology & Visual Science·Jennifer L KielczewskiHarry A Quigley
Jun 15, 2006·Alzheimer Disease and Associated Disorders·Akinori Akaike
Jun 17, 2006·The Journal of Physiology·Massimiliano Cristofanilli, Abram Akopian
Oct 3, 2006·Annual Review of Pharmacology and Toxicology·John A Dani, Daniel Bertrand
Dec 26, 2006·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Nina A DmitrievaKent T Keyser
Jul 4, 2007·The Journal of Clinical Investigation·Takayuki HaradaKohichi Tanaka
Oct 12, 2007·Neurochemistry International·María Cecilia MorenoRuth E Rosenstein
Feb 19, 2009·The Journal of Pharmacology and Experimental Therapeutics·Roger L PapkeNicole A Horenstein
Jan 15, 2010·Investigative Ophthalmology & Visual Science·Jihong WuXinghuai Sun
Apr 9, 2010·Journal of Pineal Research·Nicolás A BelforteRuth E Rosenstein
Jul 2, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nolan R CampbellDarwin K Berg
Feb 18, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kechun YangJie Wu
Mar 19, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Qing Chang, Lee J Martin
Apr 2, 2011·Lancet·Harry A Quigley
Nov 30, 2011·The Journal of Physiology·Marilena Griguoli, Enrico Cherubini
Dec 14, 2011·Progress in Retinal and Eye Research·Mohammadali AlmasiehAdriana Di Polo
Jun 1, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Adrian F LozadaDarwin K Berg
Jan 12, 2013·Investigative Ophthalmology & Visual Science·Dunja PreiserCharlotte M Poloschek
Apr 27, 2013·The British Journal of Ophthalmology·J KavithaRenuka Srinivasan
Jun 15, 2013·Investigative Ophthalmology & Visual Science·Vicki Chrysostomou, Jonathan G Crowston
Jan 25, 2014·Investigative Ophthalmology & Visual Science·Kazuhiro IwamotoCindy L Linn

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Citations

Feb 22, 2018·Proceedings of the National Academy of Sciences of the United States of America·Michael L RisnerDavid J Calkins
Apr 2, 2019·Investigative Ophthalmology & Visual Science·Leo M HallTomomi Ichinose
Aug 7, 2018·Frontiers in Neuroscience·Wanjing HuangJihong Wu
Sep 3, 2019·Experimental Eye Research·Qingchen LiChunhui Jiang

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Methods Mentioned

BETA
PCR
electrophoresis

Software Mentioned

Image J
Clampfit
Mini Analysis
Origin

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