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P2X7 receptor antagonist protects retinal ganglion cells by inhibiting microglial activation in a rat chronic ocular hypertension model

Microglial activation and the release of pro-inflammatory cytokines occur during early glaucoma. However, the exact mechanism underlying the initiation of the microglial activation process remains unclear. Thus, the present study investigated the potential role of a purine receptor subtype, the P2X...

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Autores principales: Dong, Lingdan, Hu, Yanhong, Zhou, Long, Cheng, Xianglin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783460/
https://www.ncbi.nlm.nih.gov/pubmed/29207073
http://dx.doi.org/10.3892/mmr.2017.8137
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author Dong, Lingdan
Hu, Yanhong
Zhou, Long
Cheng, Xianglin
author_facet Dong, Lingdan
Hu, Yanhong
Zhou, Long
Cheng, Xianglin
author_sort Dong, Lingdan
collection PubMed
description Microglial activation and the release of pro-inflammatory cytokines occur during early glaucoma. However, the exact mechanism underlying the initiation of the microglial activation process remains unclear. Thus, the present study investigated the potential role of a purine receptor subtype, the P2X purinoceptor 7 (P2X7) receptor, during microglial activation in the retinal tissues of a rat chronic ocular hypertension (COH) model. This was achieved by cauterizing 3 of the 4 episcleral veins. Microglial activation and caspase-1 upregulation were observed in COH rat retinas by immunohistochemical and western blotting techniques. Intravitreal injection of 2′,3′-O-(4-benzoylbenzoyl)-ATP (BzATP), a P2X7 receptor agonist, induced microglial activation in normal rat retinal tissues, which was alleviated by pretreatment with the P2X7 receptor antagonist, Brilliant Blue G (BBG). BBG further attenuated caspase-1 increment in COH rat retinal tissues. The data demonstrated that BBG reduced TUNEL-positive retinal ganglion cells in whole-mount retinal tissues with COH and normal retinal tissues following intravitreal injection with BzATP. One may conclude that the P2X7 receptor may be involved in microglial activation in the COH retina and could be considered a target for neuronal protection in glaucoma.
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spelling pubmed-57834602018-02-05 P2X7 receptor antagonist protects retinal ganglion cells by inhibiting microglial activation in a rat chronic ocular hypertension model Dong, Lingdan Hu, Yanhong Zhou, Long Cheng, Xianglin Mol Med Rep Articles Microglial activation and the release of pro-inflammatory cytokines occur during early glaucoma. However, the exact mechanism underlying the initiation of the microglial activation process remains unclear. Thus, the present study investigated the potential role of a purine receptor subtype, the P2X purinoceptor 7 (P2X7) receptor, during microglial activation in the retinal tissues of a rat chronic ocular hypertension (COH) model. This was achieved by cauterizing 3 of the 4 episcleral veins. Microglial activation and caspase-1 upregulation were observed in COH rat retinas by immunohistochemical and western blotting techniques. Intravitreal injection of 2′,3′-O-(4-benzoylbenzoyl)-ATP (BzATP), a P2X7 receptor agonist, induced microglial activation in normal rat retinal tissues, which was alleviated by pretreatment with the P2X7 receptor antagonist, Brilliant Blue G (BBG). BBG further attenuated caspase-1 increment in COH rat retinal tissues. The data demonstrated that BBG reduced TUNEL-positive retinal ganglion cells in whole-mount retinal tissues with COH and normal retinal tissues following intravitreal injection with BzATP. One may conclude that the P2X7 receptor may be involved in microglial activation in the COH retina and could be considered a target for neuronal protection in glaucoma. D.A. Spandidos 2018-02 2017-11-22 /pmc/articles/PMC5783460/ /pubmed/29207073 http://dx.doi.org/10.3892/mmr.2017.8137 Text en Copyright: © Dong et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Dong, Lingdan
Hu, Yanhong
Zhou, Long
Cheng, Xianglin
P2X7 receptor antagonist protects retinal ganglion cells by inhibiting microglial activation in a rat chronic ocular hypertension model
title P2X7 receptor antagonist protects retinal ganglion cells by inhibiting microglial activation in a rat chronic ocular hypertension model
title_full P2X7 receptor antagonist protects retinal ganglion cells by inhibiting microglial activation in a rat chronic ocular hypertension model
title_fullStr P2X7 receptor antagonist protects retinal ganglion cells by inhibiting microglial activation in a rat chronic ocular hypertension model
title_full_unstemmed P2X7 receptor antagonist protects retinal ganglion cells by inhibiting microglial activation in a rat chronic ocular hypertension model
title_short P2X7 receptor antagonist protects retinal ganglion cells by inhibiting microglial activation in a rat chronic ocular hypertension model
title_sort p2x7 receptor antagonist protects retinal ganglion cells by inhibiting microglial activation in a rat chronic ocular hypertension model
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783460/
https://www.ncbi.nlm.nih.gov/pubmed/29207073
http://dx.doi.org/10.3892/mmr.2017.8137
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