Inhibition of microRNA-155 Protects Retinal Function Through Attenuation of Inflammation in Retinal Degeneration
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Aggio-Bruce, Riemke; Chu-Tan, Joshua; Wooff, Yvette; Cioanca, Adrian; Schumann, Ulrike; Natoli, Riccardo
Description
Although extensively investigated in inflammatory conditions, the role of pro-inflammatory microRNAs (miRNAs), miR-155 and miR-146a, has not been well-studied in retinal degenerative diseases. We therefore aimed to explore the role and regulation of these miRNA in the degenerating retina, with a focus on miR-155. C57BL/6J mice were subjected to photo-oxidative damage for up to 5 days to induce focal retinal degeneration. MiR-155 expression was quantified by qRT-PCR in whole retina,...[Show more]
dc.contributor.author | Aggio-Bruce, Riemke | |
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dc.contributor.author | Chu-Tan, Joshua | |
dc.contributor.author | Wooff, Yvette | |
dc.contributor.author | Cioanca, Adrian | |
dc.contributor.author | Schumann, Ulrike | |
dc.contributor.author | Natoli, Riccardo | |
dc.date.accessioned | 2022-07-29T00:49:07Z | |
dc.date.available | 2022-07-29T00:49:07Z | |
dc.identifier.issn | 0893-7648 | |
dc.identifier.uri | http://hdl.handle.net/1885/270025 | |
dc.description.abstract | Although extensively investigated in inflammatory conditions, the role of pro-inflammatory microRNAs (miRNAs), miR-155 and miR-146a, has not been well-studied in retinal degenerative diseases. We therefore aimed to explore the role and regulation of these miRNA in the degenerating retina, with a focus on miR-155. C57BL/6J mice were subjected to photo-oxidative damage for up to 5 days to induce focal retinal degeneration. MiR-155 expression was quantified by qRT-PCR in whole retina, serum, and small-medium extracellular vesicles (s-mEVs), and a PrimeFlow™ assay was used to identify localisation of miR-155 in retinal cells. Constitutive miR-155 knockout (KO) mice and miR-155 and miR-146a inhibitors were utilised to determine the role of these miRNA in the degenerating retina. Electroretinography was employed as a measure of retinal function, while histological quantification of TUNEL+ and IBA1+ positive cells was used to quantify photoreceptor cell death and infiltrating immune cells, respectively. Upregulation of miR-155 was detected in retinal tissue, serum and s-mEVs in response to photo-oxidative damage, localising to the nucleus of a subset of retinal ganglion cells and glial cells and in the cytoplasm of photoreceptors. Inhibition of miR-155 showed increased function from negative controls and a less pathological pattern of IBA1+ cell localisation and morphology at 5 days photo-oxidative damage. While neither dim-reared nor damaged miR-155 KO animals showed retinal histological difference from controls, following photo-oxidative damage, miR-155 KO mice showed increased a-wave relative to controls. We therefore consider miR-155 to be associated with the inflammatory response of the retina in response to photoreceptor-specific degeneration. | |
dc.description.sponsorship | This work would not have been possible without the support of the National Health and Medical Research Council of Australia (NHMRC: 1127705), Retina Australia, The Gordon and Gretel Bootes Foundation and The ANU Translational Fellowship | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en_AU | |
dc.publisher | Springer Verlag | |
dc.rights | © The Author(s) 2020 | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | Molecular Neurobiology | |
dc.subject | Retina | |
dc.subject | miRNA | |
dc.subject | miR-155 | |
dc.subject | Microglia | |
dc.subject | Macrophage | |
dc.subject | Inflammation | |
dc.subject | Photo-oxidative damage | |
dc.title | Inhibition of microRNA-155 Protects Retinal Function Through Attenuation of Inflammation in Retinal Degeneration | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 58 | |
dc.date.issued | 2021 | |
local.identifier.absfor | 000000 - Internal ANU use only | |
local.identifier.ariespublication | a383154xPUB15097 | |
local.publisher.url | https://link.springer.com/ | |
local.type.status | Published Version | |
local.contributor.affiliation | Aggio-Bruce, Riemke, College of Health and Medicine, ANU | |
local.contributor.affiliation | Chu-Tan, Joshua, College of Health and Medicine, ANU | |
local.contributor.affiliation | Wooff, Yvette, College of Health and Medicine, ANU | |
local.contributor.affiliation | Cioanca, Adrian, College of Health and Medicine, ANU | |
local.contributor.affiliation | Schumann, Ulrike, College of Health and Medicine, ANU | |
local.contributor.affiliation | Natoli, Riccardo, College of Health and Medicine, ANU | |
dc.relation | http://purl.org/au-research/grants/nhmrc/1127705 | |
local.bibliographicCitation.startpage | 835 | |
local.bibliographicCitation.lastpage | 854 | |
local.identifier.doi | 10.1007/s12035-020-02158-z | |
dc.date.updated | 2021-08-01T08:24:30Z | |
local.identifier.scopusID | 2-s2.0-85092343816 | |
dcterms.accessRights | Open Access | |
dc.provenance | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | |
dc.rights.license | Creative Commons Attribution License | |
Collections | ANU Research Publications |
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