September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Large-scale microRNA expression profiling identifies retinal miRNA-mRNA signaling pathways underlying form-deprivation myopia in mice
Author Affiliations & Notes
  • Tatiana V Tkatchenko
    Ophthalmology, Columbia University, New York, New York, United States
  • Xiaoyan Luo
    Ophthalmology, Duke University, Durham, North Carolina, United States
  • Andrei V Tkatchenko
    Ophthalmology, Columbia University, New York, New York, United States
    Pathology & Cell Biology, Columbia University, New York, New York, United States
  • Candida Vaz
    Bioinformatics Institute, Agency for Science Technology and Research, Singapore, Singapore
  • Vivek M Tanavde
    Bioinformatics Institute, Agency for Science Technology and Research, Singapore, Singapore
    Institute for Medical Biology, A*STAR, Singapore, Singapore
  • Sebastian Maurer-Stroh
    Bioinformatics Institute, Agency for Science Technology and Research, Singapore, Singapore
  • Stefan Zauscher
    Mechanical Engineering and Materials Science, Duke University, Durham, North Carolina, United States
  • Pedro Gonzalez
    Ophthalmology, Duke University, Durham, North Carolina, United States
  • Terri L Young
    Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin, United States
  • Footnotes
    Commercial Relationships   Tatiana Tkatchenko, None; Xiaoyan Luo, None; Andrei Tkatchenko, None; Candida Vaz, None; Vivek Tanavde, None; Sebastian Maurer-Stroh, None; Stefan Zauscher, None; Pedro Gonzalez, None; Terri Young, None
  • Footnotes
    Support  NIH Grants R01EY023839, R01EY023287, R01EY016228, R01EY014685, P30EY019007. Duke Eye Center Exploring Grant, unrestricted funds from Research to Prevent Blindness (New York, NY) to the Department of Ophthalmology, Columbia University and the Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Acquavella Family Foundation, Joseph C. Connors, and the University of Wisconsin Centennial Scholar Fund.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4837. doi:
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      Tatiana V Tkatchenko, Xiaoyan Luo, Andrei V Tkatchenko, Candida Vaz, Vivek M Tanavde, Sebastian Maurer-Stroh, Stefan Zauscher, Pedro Gonzalez, Terri L Young; Large-scale microRNA expression profiling identifies retinal miRNA-mRNA signaling pathways underlying form-deprivation myopia in mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4837.

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

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Abstract

Purpose : Postnatal refractive eye development is regulated by a vision-driven signaling cascade originating in the retina. Failure of this process often leads to the development of myopia associated with changes in ocular tissue gene expression. Although differential expression of coding genes underlying development of myopia has been a subject of intense investigation, the role of non-coding genes such as microRNAs in refractive eye development and in the development of myopia is largely unknown. In this study we explored myopia-associated miRNA expression profiles in the retina and sclera of mice with experimental myopia using microarrays.

Methods : Twelve P24 C57BL/6J mice were subjected to 10 days of monocular visual form deprivation. Total RNA was isolated from the retina and sclera of myopic and control eyes using mirVana miRNA isolation kit (Life Technologies, Grand Island, NY) according to the manufacturer’s instructions. MiRNA expression profiling was carried out using Agilent Mouse microRNA Microarray (release 12.0) (Agilent Technologies, Santa Clara, CA). Raw gene expression data were normalized using quantile normalization procedure, and log2-transformed. This was followed by the removal of absent features and outliers. The normalized data were then analyzed using ANOVA to identify differences in miRNA expression levels between myopic and control eyes. Differentially expressed miRNAs were identified using an FDR-adjusted P-value threshold of 0.05 and a cutoff of 2-fold change in expression.

Results : We found a total of 53 differentially expressed miRNAs in the retina and no differences in miRNA expression in the sclera of C57BL/6J mice after 10 days of visual form deprivation, which induced -6.93 ± 2.44 D (P < 0.000001, n = 12) of myopia. We also identified their putative mRNA targets among mRNAs found to be differentially expressed in myopic retina and potential signaling pathways involved in the development of form-deprivation myopia using miRNA-mRNA interaction network analysis. Analysis of myopia-associated signaling pathways revealed that myopic response to visual form deprivation in the retina is regulated by a small number of highly integrated signaling pathways.

Conclusions : Our findings highlight extensive involvement of miRNAs in the regulation of refractive eye development, and in the development of myopia through the retinal gene regulation.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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