P2X7 receptor antagonists protect against N-methyl-D-aspartic acid-induced neuronal injury in the rat retina

European Journal of Pharmacology
Kenji SakamotoKunio Ishii

Abstract

Activation of N-methyl-d-aspartic acid (NMDA) receptors followed by a large Ca(2+) influx is thought to be a mechanism of glaucoma-induced neuronal cell death. It is possible that damage-associated molecular patterns leak from injured cells, such as adenosine triphosphate, causing retinal ganglion cell death in glaucoma. In the present study, we histologically investigated whether antagonists of the P2X7 receptor protected against NMDA-induced retinal injury in the rat in vivo. Under ketamine/xylazine anesthesia, male Sprague-Dawley rats were subjected to intravitreal injection of NMDA. We used A438079 (3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methyl pyridine) and brilliant blue G as P2X7 receptor antagonists. Upon morphometric evaluation 7 days after an intravitreal injection (200 nmol/eye), NMDA-induced cell loss was apparent in the ganglion cell layer. Intravitreal A438079 (50 pmol/eye) simultaneously injected with NMDA and intraperitoneal brilliant blue G (50 mg/kg) administered just before the NMDA injection as well as 24 and 48h after significantly reduced cell loss. In addition, A438079 decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells 12h after NMDA injection. P2X7 rec...Continue Reading

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Citations

Apr 20, 2016·European Journal of Pharmacology·Nucci CarloMorrone Luigi Antonio
Oct 19, 2016·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Kenneth A Jacobson, Mortimer M Civan
Dec 9, 2016·Scientific Reports·Francisco M Nadal-NicolásMarta Agudo-Barriuso
Feb 29, 2020·Cells·Stéphane Mélik ParsadaniantzChristophe Baudouin
Jul 18, 2020·Medicinal Research Reviews·Francesco CalzaferriAntonio G García
Oct 11, 2017·Frontiers in Pharmacology·Geoffrey Burnstock
May 1, 2019·International Journal of Molecular Sciences·Sofia PavlouMei Chen
Feb 2, 2021·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Eleonora SpinozziPetrelli Riccardo
Jul 3, 2021·Frontiers in Pharmacology·Shan-Shan YeJian-Tao Song

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