July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
MicroRNA-223 regulates neuroinflammation in retinal degenerations
Author Affiliations & Notes
  • Nilisha Fernando
    John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia
  • Josephine Wong
    John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia
  • Riemke Aggio-Bruce
    John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia
  • Yvette Wooff
    John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia
    ANU Medical School, The Australian National University, Canberra, Australian Capital Territory, Australia
  • Riccardo Carlo Natoli
    John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia
    ANU Medical School, The Australian National University, Canberra, Australian Capital Territory, Australia
  • Footnotes
    Commercial Relationships   Nilisha Fernando, None; Josephine Wong, None; Riemke Aggio-Bruce, None; Yvette Wooff, None; Riccardo Natoli, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4001. doi:
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      Nilisha Fernando, Josephine Wong, Riemke Aggio-Bruce, Yvette Wooff, Riccardo Carlo Natoli; MicroRNA-223 regulates neuroinflammation in retinal degenerations. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4001.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Excessive inflammation is implicated in neurodegenerative diseases including Age-Related Macular Degeneration (AMD). Regulation of pro-inflammatory cytokine release (including IL-1β) by microglia and macrophages is critical in preventing photoreceptor loss. MicroRNAs (miRNAs) have the ability to target the expression of multiple genes, often within associated pathways. However, there is still a poor understanding of the role of miRNAs in controlling inflammation in the retina. MicroRNA-223 (miR-223) dysregulation has been linked to the progression of neuroinflammatory diseases, although its retinal expression has not been previously studied. Here, we investigated the role of miR-223 in inflammation and cell death using a model of retinal degenerations.

Methods : C57BL/6J mice were exposed to photo-oxidative damage (PD), and eyes and retinas were collected for cell death (TUNEL), immunohistochemistry (IBA1) and qPCR for miR-223 and inflammatory gene expression (Il-1β, Nlrp3, Ccl3, Il-6). Mice with no exposure to PD were used as dim-reared controls. In vitro, miR-223 expression in immortalised and primary cell cultures (microglia, Müller cells, RPE, photoreceptors) was determined via qPCR, following inflammatory stimulation. A miR-223 inhibitor was intravitreally injected into PD mice to determine the effect on photoreceptor loss.

Results : Retinal miR-223 expression increased significantly during PD, compared to dim-reared controls (P<0.05). This was associated with an increase in Il-1β expression in PD (P<0.05), as well as dysregulation of Nlrp3, Ccl3 and Il-6 genes in PD (predicted targets of miR-223, P<0.05). In vitro, in stimulated C8B4 immortalised and primary retinal microglia, miR-223 expression was significantly decreased alongside an increase in Il-1β (P<0.05). Conversely, miR-223 was upregulated significantly in 661W photoreceptor-like cells following PD (P<0.05). Injection of a miR-223 inhibitor increased photoreceptor loss in PD (P<0.05).

Conclusions : It is hypothesised that in the retina, photoreceptors express miR-223 and potentially regulate inflammation at the cellular source in microglia and macrophages. Further investigation into the vast array of inflammatory pathways targeted by miR-223 could shed light on novel mechanisms of miR-223 activity in retinal degenerations, including neuroprotection. Regulating miR-223 using mimics may be of therapeutic benefit for neurodegenerative diseases including AMD.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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