June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
MiR-30a-5p inhibition prevents neovascularization through CCL2 upregulation and microglia activation in a model of ischemic retinopathy
Author Affiliations & Notes
  • Salome Murinello
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Yoshihiko Usui
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
    Tokyo Medical University, Tokyo, Japan
  • Susumu Sakimoto
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Maki Kitano
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Edith Aguilar
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Martin Friedlander
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Footnotes
    Commercial Relationships   Salome Murinello, None; Yoshihiko Usui, None; Susumu Sakimoto, None; Maki Kitano, None; Edith Aguilar, None; Martin Friedlander, None
  • Footnotes
    Support  ADA postdoctoral fellowship 1-16-PDF-072
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5383. doi:
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      Salome Murinello, Yoshihiko Usui, Susumu Sakimoto, Maki Kitano, Edith Aguilar, Martin Friedlander; MiR-30a-5p inhibition prevents neovascularization through CCL2 upregulation and microglia activation in a model of ischemic retinopathy
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):5383.

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

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Abstract

Purpose : The vast majority of blinding diseases are associated with abnormal angiogenesis. MicroRNA-30a-5p (miR-30a) was previously identified as a pro-angiogenic miRNA. Interestingly this miRNA is highly expressed in the retina, particularly by microglia. We hypothesized that miR-30a-5p inhibition may prevent neovascularization (NV) in the oxygen-induced retinopathy (OIR) model of ischemic injury by modulating microglial function.

Methods : The relevance of miR-30a in the OIR model was confirmed by determining its expression levels at several key time points (p12, p14, p17, p21) by qPCR. To assess the effects of inhibiting miR-30a in OIR, a single intravitreous injection of anti-miR-30a or a scramble control was performed at p12 and retinas were collected for immunohistochemical quantification of NV at p17. Changes in microglia activation were assessed by IHC for CD11b. Changes in potential miR-30a targets were assessed by qPCR.

Results : MiR-30a was upregulated at p12 and p14, and downregulated at p17 and p21 in OIR mice, when compared to normoxic controls. Injection of anti-miR30a significantly inhibited neovascularization in OIR. Surprisingly, anti-miR-30a injection resulted in microglial activation and migration towards vaso-obliterated areas. Consistently, retinal levels of a chemokine known to mediate recruitment of myeloid cells, CCL2, were upregulated.

Conclusions : The data presented here show that inhibition of a miR-30a can lead to reduced levels of retinal angiogenesis in a model of ischemic retinopathy by inducing microglia activation and increasing CCL2 levels, a known pro-inflammatory chemokine. These paradoxical results highlight the need for a better understanding of neuroinflammatory mechanisms in the retina, and suggest anti-miR-30a as a key modulator of microglia function.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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