July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
MicroRNA-124 is redistributed from neurons to glia to reduce inflammation and slow progressive retinal degeneration
Author Affiliations & Notes
  • Joshua Aaron Chu-Tan
    Neuroscience, The John Curtin School of Medical Research, ANU, Canberra, Australian Capital Territory, Australia
  • Matt Rutar
    Neuroscience, The John Curtin School of Medical Research, ANU, Canberra, Australian Capital Territory, Australia
  • Kartik Saxena
    Neuroscience, The John Curtin School of Medical Research, ANU, Canberra, Australian Capital Territory, Australia
  • Riemke Aggio-Bruce
    Neuroscience, The John Curtin School of Medical Research, ANU, Canberra, Australian Capital Territory, Australia
  • Rohan W. Essex
    Academic Unit of Ophthalmology, The Australian National University, Canberra, Australian Capital Territory, Australia
  • Krisztina Valter
    Neuroscience, The John Curtin School of Medical Research, ANU, Canberra, Australian Capital Territory, Australia
    The Australian National University Medical School, Canberra, Australian Capital Territory, Australia
  • Haihan Jiao
    Neuroscience, The John Curtin School of Medical Research, ANU, Canberra, Australian Capital Territory, Australia
  • Michele C Madigan
    Save Sight Institute, The University of Sydney, Sydney, New South Wales, Australia
    School of Optometry and Vision Science, The University of New South Wales, Canberra, New South Wales, Australia
  • Jan Provis
    Neuroscience, The John Curtin School of Medical Research, ANU, Canberra, Australian Capital Territory, Australia
    The Australian National University Medical School, Canberra, Australian Capital Territory, Australia
  • Riccardo Natoli
    Neuroscience, The John Curtin School of Medical Research, ANU, Canberra, Australian Capital Territory, Australia
    The Australian National University Medical School, Canberra, Australian Capital Territory, Australia
  • Footnotes
    Commercial Relationships   Joshua Chu-Tan, None; Matt Rutar, None; Kartik Saxena, None; Riemke Aggio-Bruce, None; Rohan Essex, None; Krisztina Valter, None; Haihan Jiao, None; Michele Madigan, None; Jan Provis, None; Riccardo Natoli, None
  • Footnotes
    Support  Australia NHMRC Project Grant (APP1127705, 2017-2019), Gretel and Gordon Bootes Foundation Grant (2013), Ophthalmic Research Institute of Australia/Eye Surgeons’ Foundation Grant (2015)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4604. doi:https://doi.org/
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      Joshua Aaron Chu-Tan, Matt Rutar, Kartik Saxena, Riemke Aggio-Bruce, Rohan W. Essex, Krisztina Valter, Haihan Jiao, Michele C Madigan, Jan Provis, Riccardo Natoli; MicroRNA-124 is redistributed from neurons to glia to reduce inflammation and slow progressive retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4604. doi: https://doi.org/.

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

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Abstract

Purpose : MicroRNA-124 (miR-124) is highly expressed in neurons and is largely considered to be involved in neuronal development. MiR-124 has also been shown to act as a powerful anti-inflammatory molecule, regulating the expression of pro-inflammatory chemokine, CCL2. However, the role of miR-124 in the degenerating retina is not well established. We sought to determine the cellular location and function of miR-124 in the degenerating retina and demonstrate its potential for reducing retinal inflammation and slowing focal degeneration.

Methods : In situ hybridization was used to localize the expression of miR-124 in AMD tissue, as well as rodent retinae after photo-oxidative damage (PD, 100K lux, 5 days). Luciferase assays using the 3’UTR vector for Ccl2 were performed in vitro for miR-124 target validation in retinal cells. MiR-124 mimics were delivered intravitreally, and following 5 day PD, retinae were assessed for photoreceptor cell death (TUNEL), gene expression (qRT-PCR), histology (immunohistochemistry) and function (electroretinography).

Results : In both AMD tissue and PD rodent tissue, expression of miR-124 decreased compared to age-matched healthy and dim-reared specimen respectively. MiR-124 was localized to both neuronal and glial (Müller) cells, and redistributed from Müller cell end feet to the Müller cell bodies (inner nuclear layer) following degeneration. In isolated Müller cells, we showed abundant expression of miR-124 in normal rodent retina with a decrease in expression levels following PD (P<0.05). Intravitreal delivery of miR-124 mimics, compared to a scrambled miRNA treatment, reduced retinal Ccl2 expression and mononuclear phagocyte infiltration, concurrent with improved retinal function (P<0.05). We also confirmed Ccl2 as one of the targets of miR-124 in retinal cells.

Conclusions : We have demonstrated that the anti-inflammatory microRNA, miR-124, is redistributed within the retinal layers, from neuronal to glial, following retinal degeneration. Further, we show that reduced expression of miR-124 is correlated with disease progression, and that increasing availability of miR-124 reduces retinal inflammation. This work validates the use of miR-124 as a potential therapeutic for neurodegenerative diseases where inflammation is a facet, such as Age-Related Macular Degeneration (AMD).

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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