{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:59:07Z","timestamp":1782280747961,"version":"3.54.5"},"posted":{"date-parts":[[2024,6,1]]},"group-title":"Neuroscience","reference-count":68,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Glaucoma is a neurodegenerative disease that leads to the death of retinal ganglion cells (RGCs). A growing body of literature suggests a role for neuroinflammation in RGC death after glaucoma-relevant insults. For instance, it was shown that deficiency of three proinflammatory cytokines, complement component 1, subcomponent q (\n                  <jats:italic>C1q<\/jats:italic>\n                  ), interleukin 1 alpha (\n                  <jats:italic>Il1a<\/jats:italic>\n                  ), and tumor necrosis factor (\n                  <jats:italic>Tnf<\/jats:italic>\n                  ), resulted in near complete protection of RGCs after two glaucoma-relevant insults, optic nerve injury and ocular hypertension. While TNF and C1Q have been extensively investigated in glaucoma-relevant model systems, the role of IL1A in RGC is not as well defined. Thus, we investigated the direct neurotoxicity of IL1A on RGCs in vivo. Intravitreal injection of IL1A did not result in RGC death at either 14 days or 12 weeks after insult. Consistent with previous studies, TNF injection did not result in significant RGC loss at 14 days but did after 12 weeks. Interestingly, IL1A+TNF resulted in a relatively rapid RGC death, driving significant RGC loss two weeks after injection. JUN activation and SARM1 have been implicated in RGC death in glaucoma and after cytokine insult. Using mice deficient in JUN or SARM1, we show RGC loss after IL1A+TNF insult is JUN-independent and SARM1-dependent. Furthermore, RNA-seq analysis showed that RGC death by SARM1 deficiency does not stop the neuroinflammatory response to IL1A+TNF. These findings indicate that IL1A can potentiate TNF-induced RGC death after combined insult is likely driven by a SARM1-dependent RGC intrinsic signaling pathway.\n                <\/jats:p>","DOI":"10.1101\/2024.05.28.596328","type":"posted-content","created":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T21:25:14Z","timestamp":1717277114000},"source":"Crossref","is-referenced-by-count":1,"title":["IL1A enhances TNF-induced retinal ganglion cell death"],"prefix":"10.64898","author":[{"given":"Katherine M.","family":"Andersh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"MacLean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0565-6474","authenticated-orcid":false,"given":"Gareth R.","family":"Howell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2844-7632","authenticated-orcid":false,"given":"Richard T.","family":"Libby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024060413050615000_2024.05.28.596328v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.07.002"},{"key":"2024060413050615000_2024.05.28.596328v1.2","doi-asserted-by":"crossref","first-page":"100998","DOI":"10.1016\/j.preteyeres.2021.100998","article-title":"Molecular regulation of neuroinflammation in glaucoma: Current knowledge and the ongoing search for new treatment targets","volume":"87","year":"2022","journal-title":"Prog Retin Eye Res"},{"key":"2024060413050615000_2024.05.28.596328v1.3","doi-asserted-by":"crossref","first-page":"101169","DOI":"10.1016\/j.preteyeres.2023.101169","article-title":"Activation of retinal glial cells contributes to the degeneration of ganglion cells in experimental glaucoma","volume":"93","year":"2023","journal-title":"Prog Retin Eye Res"},{"key":"2024060413050615000_2024.05.28.596328v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029"},{"key":"2024060413050615000_2024.05.28.596328v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107776"},{"issue":"5","key":"2024060413050615000_2024.05.28.596328v1.6","doi-asserted-by":"crossref","first-page":"108271","DOI":"10.1016\/j.celrep.2020.108271","article-title":"GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension","volume":"33","year":"2020","journal-title":"Cell Rep"},{"issue":"7883","key":"2024060413050615000_2024.05.28.596328v1.7","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41586-021-03960-y","article-title":"Neurotoxic reactive astrocytes induce cell death via saturated lipids","volume":"599","year":"2021","journal-title":"Nature"},{"key":"2024060413050615000_2024.05.28.596328v1.8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44646"},{"key":"2024060413050615000_2024.05.28.596328v1.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035495"},{"key":"2024060413050615000_2024.05.28.596328v1.10","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2801-06.2006"},{"issue":"194","key":"2024060413050615000_2024.05.28.596328v1.11","first-page":"1","article-title":"Tumor necrosis factor alpha has an early protective effect on retinal ganglion cells after optic nerve crush","volume":"11","year":"2015","journal-title":"Journal of Neuroinflammation"},{"key":"2024060413050615000_2024.05.28.596328v1.12","doi-asserted-by":"crossref","unstructured":"Ko KW , Milbrandt J , DiAntonio A . 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