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dc.contributor.authorNatoli, R
dc.contributor.authorFernando, N
dc.contributor.authorMadigan, M
dc.contributor.authorChu-Tan, JA
dc.contributor.authorValter, K
dc.contributor.authorProvis, J
dc.contributor.authorRutar, M
dc.date.accessioned2021-02-04T00:44:08Z
dc.date.available2021-02-04T00:44:08Z
dc.date.issued2017-04-24
dc.identifierpii: 10.1186/s13024-017-0175-y
dc.identifier.citationNatoli, R., Fernando, N., Madigan, M., Chu-Tan, J. A., Valter, K., Provis, J. & Rutar, M. (2017). Microglia- derived IL-1 beta promotes chemokine expression by Muller cells and RPE in focal retinal degeneration. MOLECULAR NEURODEGENERATION, 12 (1), https://doi.org/10.1186/s13024-017-0175-y.
dc.identifier.issn1750-1326
dc.identifier.urihttp://hdl.handle.net/11343/259178
dc.description.abstractBACKGROUND: Chemokine signalling is required for the homing of leukocytes during retinal inflammation, and is associated with pathogenesis of diseases such as age-related macular degeneration (AMD). Here, we explore the role of interleukin-1β (IL-1β) in modulating AMD-associated chemokines Ccl2, Cxcl1, and Cxcl10 during photo-oxidative retinal damage, and the effect on both the accumulation of outer-retinal macrophages, and death of photoreceptors. METHODS: Inhibition of retinal IL-1β expression was performed using either siRNA or antibody neutralisation, which was intravitreally injected in SD rats prior to photo-oxidative damage. Changes in the expression and localisation of Il-1β, Ccl2, Cxcl1 and Cxcl10 genes were assessed using qPCR and in situ hybridisation, while the recruitment of retinal macrophages was detected using immunohistochemistry for IBA1. Levels of photoreceptor cell death were determined using TUNEL. RESULTS: Photo-oxidative damage elevated the expression of Il-1β and inflammasome-related genes, and IL-1β protein was detected in microglia infiltrating the outer retina. This was associated with increased expression of Ccl2, Cxcl1, and Cxcl10. Intravitreal IL-1β inhibitors suppressed chemokine expression following damage and reduced macrophage accumulation and photoreceptor death. Moreover, in Müller and RPE cell cultures, and in vivo, Ccl2, Cxcl1 and Cxcl10 were variously upregulated when stimulated with IL-1β, with increased macrophage accumulation detected in vivo. CONCLUSIONS: IL-1β is produced by retinal microglia and macrophages and promotes chemokine expression by Müller cells and RPE in retinal degeneration. Targeting IL-1β may prove efficacious in broadly suppressing chemokine-mediated inflammation in retinal dystrophies such as AMD.
dc.languageEnglish
dc.publisherBIOMED CENTRAL LTD
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleMicroglia- derived IL-1 beta promotes chemokine expression by Muller cells and RPE in focal retinal degeneration
dc.typeJournal Article
dc.identifier.doi10.1186/s13024-017-0175-y
melbourne.affiliation.departmentAnatomy and Neuroscience
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleMolecular Neurodegeneration
melbourne.source.volume12
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1205423
melbourne.contributor.authorRutar, Matthew
dc.identifier.eissn1750-1326
melbourne.accessrightsOpen Access


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