{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:41:54Z","timestamp":1788586914271,"version":"build-2803163510"},"reference-count":75,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009982","name":"Humane Research Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009982","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Norwich Glaucoma Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u00b5M; 36 h) significantly increased the secretion of IL-1\u03b2 and IL-10. IL-1\u03b2 was selected for further investigation. BzATP (100 \u00b5M) caused an increase in the expression and release of IL-1\u03b2 in a time-dependent manner; this increase was inhibited through a co-incubation with BBG (1 \u00b5M). Exogenous IL-1\u03b2 alone (10 ng\/mL) did not cause a loss of RGCs. However, IL-1\u03b2 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-1\u03b2 mediated. Furthermore, IL-1\u03b2 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-1\u03b2 in the human retina and supports the role of the ATP\/P2X7\/IL-1\u03b2 axis in RGC survival and possible glaucomatous RGC degeneration.<\/jats:p>","DOI":"10.3390\/ijms262110345","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:47:36Z","timestamp":1761266856000},"page":"10345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The P2X7 Receptor Regulates IL-1\u03b2 Secretion in the Human Retina"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3498-264X","authenticated-orcid":false,"given":"Nuwan","family":"Niyadurupola","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Colney Lane, Norwich NR4 7UY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sidaway","sequence":"additional","affiliation":[{"name":"School of Chemistry, Pharmacy and Pharmacology, University of East Anglia, Norwich NR4 7TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Broadway","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Colney Lane, Norwich NR4 7UY, UK"},{"name":"School of Chemistry, Pharmacy and Pharmacology, University of East Anglia, Norwich NR4 7TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Sanderson","sequence":"additional","affiliation":[{"name":"School of Chemistry, Pharmacy and Pharmacology, University of East Anglia, Norwich NR4 7TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/5584_2017_59","article-title":"The P2X7 Receptor","volume":"1051","author":"Sluyter","year":"2017","journal-title":"Adv. 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