Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout

Abstract There is increasing evidence for the vulnerability of specific retinal ganglion cell (RGC) types in those with glaucoma and in animal models. In addition, the P2X7-receptor (P2X7-R) has been suggested to contribute to RGC death following stimulation and elevated IOP, though its role in RGC...

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Autores principales:	Anna Y. M. Wang, Vickie H. Y. Wong, Pei Ying Lee, Bang V. Bui, Stefanie Dudczig, Kirstan A. Vessey, Erica L. Fletcher
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d9083722c2204c03bafe2c974c82c662
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spelling	oai:doaj.org-article:d9083722c2204c03bafe2c974c82c6622021-12-02T10:54:06ZRetinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout10.1038/s41598-021-83669-02045-2322https://doaj.org/article/d9083722c2204c03bafe2c974c82c6622021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83669-0https://doaj.org/toc/2045-2322Abstract There is increasing evidence for the vulnerability of specific retinal ganglion cell (RGC) types in those with glaucoma and in animal models. In addition, the P2X7-receptor (P2X7-R) has been suggested to contribute to RGC death following stimulation and elevated IOP, though its role in RGC dysfunction prior to death has not been examined. Therefore, we examined the effect of an acute, non-ischemic intraocular pressure (IOP) insult (50 mmHg for 30 min) on RGC function in wildtype mice and P2X7-R knockout (P2X7-KO) mice. We examined retinal function using electroretinogram recordings and individual RGC responses using multielectrode arrays, 3 days following acute IOP elevation. Immunohistochemistry was used to examine RGC cell death and P2X7-R expression in several RGC types. Acute intraocular pressure elevation produced pronounced dysfunction in RGCs; whilst other retinal neuronal responses showed lesser changes. Dysfunction at 3 days post-injury was not associated with RGC loss or changes in receptive field size. However, in wildtype animals, OFF-RGCs showed reduced spontaneous and light-elicited activity. In the P2X7-KO, both ON- and OFF-RGC light-elicited responses were reduced. Expression of P2X7-R in wildtype ON-RGC dendrites was higher than in other RGC types. In conclusion, OFF-RGCs were vulnerable to acute IOP elevation and their dysfunction was not rescued by genetic ablation of P2X7-R. Indeed, knockout of P2X7-R also caused ON-RGC dysfunction. These findings aid our understanding of how pressure affects RGC function and suggest treatments targeting the P2X7-R need to be carefully considered.Anna Y. M. WangVickie H. Y. WongPei Ying LeeBang V. BuiStefanie DudczigKirstan A. VesseyErica L. FletcherNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Y. M. Wang Vickie H. Y. Wong Pei Ying Lee Bang V. Bui Stefanie Dudczig Kirstan A. Vessey Erica L. Fletcher Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout
description	Abstract There is increasing evidence for the vulnerability of specific retinal ganglion cell (RGC) types in those with glaucoma and in animal models. In addition, the P2X7-receptor (P2X7-R) has been suggested to contribute to RGC death following stimulation and elevated IOP, though its role in RGC dysfunction prior to death has not been examined. Therefore, we examined the effect of an acute, non-ischemic intraocular pressure (IOP) insult (50 mmHg for 30 min) on RGC function in wildtype mice and P2X7-R knockout (P2X7-KO) mice. We examined retinal function using electroretinogram recordings and individual RGC responses using multielectrode arrays, 3 days following acute IOP elevation. Immunohistochemistry was used to examine RGC cell death and P2X7-R expression in several RGC types. Acute intraocular pressure elevation produced pronounced dysfunction in RGCs; whilst other retinal neuronal responses showed lesser changes. Dysfunction at 3 days post-injury was not associated with RGC loss or changes in receptive field size. However, in wildtype animals, OFF-RGCs showed reduced spontaneous and light-elicited activity. In the P2X7-KO, both ON- and OFF-RGC light-elicited responses were reduced. Expression of P2X7-R in wildtype ON-RGC dendrites was higher than in other RGC types. In conclusion, OFF-RGCs were vulnerable to acute IOP elevation and their dysfunction was not rescued by genetic ablation of P2X7-R. Indeed, knockout of P2X7-R also caused ON-RGC dysfunction. These findings aid our understanding of how pressure affects RGC function and suggest treatments targeting the P2X7-R need to be carefully considered.
format	article
author	Anna Y. M. Wang Vickie H. Y. Wong Pei Ying Lee Bang V. Bui Stefanie Dudczig Kirstan A. Vessey Erica L. Fletcher
author_facet	Anna Y. M. Wang Vickie H. Y. Wong Pei Ying Lee Bang V. Bui Stefanie Dudczig Kirstan A. Vessey Erica L. Fletcher
author_sort	Anna Y. M. Wang
title	Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout
title_short	Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout
title_full	Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout
title_fullStr	Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout
title_full_unstemmed	Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout
title_sort	retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by p2x7 receptor knockout
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d9083722c2204c03bafe2c974c82c662
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Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout

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