June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
MicroRNA expression array analysis in a mouse model of oxygen-induced retinopathy
Author Affiliations & Notes
  • Ricky Zhenghao Cui
    Mayo Medical School, Rochester, MN
    Ophthalmology, Boston Children's Hospital, Boston, MA
  • Chi-Hsiu Liu
    Ophthalmology, Boston Children's Hospital, Boston, MA
  • Aimee Marie Juan
    University of Pennsylvania School of Medicine, Philadelphia, PA
  • Lucy Evans
    Ophthalmology, Boston Children's Hospital, Boston, MA
  • Katherine Tian
    Ophthalmology, Boston Children's Hospital, Boston, MA
  • Jing Chen
    Ophthalmology, Boston Children's Hospital, Boston, MA
  • Footnotes
    Commercial Relationships Ricky Cui, None; Chi-Hsiu Liu, None; Aimee Juan, None; Lucy Evans, None; Katherine Tian, None; Jing Chen, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 47. doi:
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      Ricky Zhenghao Cui, Chi-Hsiu Liu, Aimee Marie Juan, Lucy Evans, Katherine Tian, Jing Chen; MicroRNA expression array analysis in a mouse model of oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):47.

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

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Abstract

Purpose: Retinopathy of prematurity (ROP) is a leading cause of blindness in children. To improve upon current invasive surgical treatments, a better understanding of the molecular control systems in the pathogenesis of ROP is needed to identify preventative and less-invasive therapies. MicroRNAs (miRNAs), a group of small non-coding regulatory RNAs, have been shown to play critical roles in both vascular and neuronal development of retina, as well as in pathologic angiogenesis. Here we assess the expression profile of retinal microRNAs in a mouse model of oxygen-induced retinopathy (OIR) modeling ROP in humans, in an effort to identify the function and therapeutic potential of specific microRNAs in retinopathy.

Methods: Neonatal C57BL/6J mice were exposed to 75% oxygen from postnatal (P) 7 to P 12 to induce retinopathy. MicroRNA expression array analysis (Affymetrix GeneChip miRNA array) was used to assess miRNA expression profile in P17 OIR retinas compared to age-matched room air control retinas (n=3 per group). Selected miRNAs were validated with RT-qPCR. Putative target genes of significantly altered miRNAs were analyzed with softwares Targetscan and miRbase.

Results: We identified more than 20 microRNAs that are significantly upregulated in OIR retinas and more than 20 miRNAs that are downregulated. Upregulated miRNAs include miR-351, miR-762, miR-210, miR-145 and miR-214. Downregulated miRNAs include miR-129-5p, miR-129-3p, miR-150, miR-203, and miR-375. In particular, the expression of miR-150 is significantly suppressed up to 5 fold in OIR retinas compared to age matched room air controls as confirmed by qRT-PCR (n = 6 per group, p ≤ 0.05). Bioinformatics analysis showed that multiple regulated miRNAs have predicted target genes in angiogenic and/or inflammatory pathways.

Conclusions: Our findings indicate that multiple miRNAs are significantly altered in OIR retinas, which may exert critical post-transcriptional regulatory roles in pathological retinal neovascularization through potentially influencing angiogenesis and inflammation processes important for retinopathy. Further analysis of these miRNAs will help determine their function and therapeutic potential in ROP.

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