The P2X7 receptor regulates IL-1β secretion in the human retina

Niyadurupola, Nuwan, Sidaway, Peter, Broadway, David C. and Sanderson, Julie (2025) The P2X7 receptor regulates IL-1β secretion in the human retina. International Journal of Molecular Medicine, 26 (21). ISSN 1107-3756

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Abstract

The P2X7 receptor has been associated with the neurodegeneration of retinal ganglion cells (RGCs), which is central to the loss of vision in glaucoma. Furthermore, the activation of P2X7 has been shown to cause the death of RGCs, including in the human retina. Human organotypic retinal cultures (HORCs) were used to investigate the potential indirect mechanisms of RGC death. Of the 27 cytokine/growth factors assayed, the stimulation of P2X7 using BzATP (100 µM; 36 h) significantly increased the secretion of IL-1β and IL-10. IL-1β was selected for further investigation. BzATP (100 µM) caused an increase in the expression and release of IL-1β in a time-dependent manner; this increase was inhibited through a co-incubation with BBG (1 µM). Exogenous IL-1β alone (10 ng/mL) did not cause a loss of RGCs. However, IL-1β inhibited the loss of RGCs caused by BzATP, and this neuroprotection was prevented by the Interleukin-1 receptor-1 antagonist (IL-1ra) (100 ng/mL). The IL1 receptor IL-1R1 was localised to the inner retina close to the RGCs, although not predominantly co-localised with RGC bodies. The results suggest that the P2X7-mediated death of RGCs is not IL-1β mediated. Furthermore, IL-1β may be upregulated as part of a response to mitigate P2X7-mediated damage to the retina. Our research is the first to indicate the P2X7-mediated regulation of IL-1β in the human retina and supports the role of the ATP/P2X7/IL-1β axis in RGC survival and possible glaucomatous RGC degeneration.

Item Type:	Article
Additional Information:	Data Availability Statement: The data that support the findings of this study are available upon request from the corresponding author. Funding: The Humane Research Trust, The Norwich Glaucoma Research Fund.
Uncontrolled Keywords:	p2x7,interleukin1-beta,neuroinflammation,human organotypic retinal cultures,retina,glaucoma,molecular biology,spectroscopy,catalysis,inorganic chemistry,computer science applications,physical and theoretical chemistry,organic chemistry ,/dk/atira/pure/subjectarea/asjc/1300/1312
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
UEA Research Groups:	Faculty of Science > Research Groups > Molecular and Tissue Pharmacology
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	03 Dec 2025 16:30
Last Modified:	03 Dec 2025 16:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101231
DOI:	10.3390/ijms262110345

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