July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Gene expression profiling in the retina of Collaborative Cross mice reveals pathways underlying refractive eye development and susceptibility to myopia
Author Affiliations & Notes
  • Tatiana V Tkatchenko
    Ophthalmology, Columbia University, New York, New York, United States
  • Andrei V Tkatchenko
    Ophthalmology, Columbia University, New York, New York, United States
    Pathology and Cell Biology, Columbia University, New York, New York, United States
  • Footnotes
    Commercial Relationships   Tatiana Tkatchenko, None; Andrei Tkatchenko, Columbia University (P)
  • Footnotes
    Support  NIH/NEI grant R01EY023839; Unrestricted funds from Research to Prevent Blindness (New York, NY) to the Department of Ophthalmology, Columbia University.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 698. doi:
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    • Get Citation

      Tatiana V Tkatchenko, Andrei V Tkatchenko; Gene expression profiling in the retina of Collaborative Cross mice reveals pathways underlying refractive eye development and susceptibility to myopia. Invest. Ophthalmol. Vis. Sci. 2018;59(9):698.

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

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Abstract

Purpose : Human population studies suggest that genetic factors play important role in refractive error development; however, genetic pathways underlying refractive eye development and susceptibility to myopia remain obscure. The purpose of this study was to identify genetic pathways underlying refractive eye development and susceptibility to myopia in mice.

Methods : Normal refractive eye development and susceptibility to form-deprivation myopia was analyzed in 8 genetically distant mouse strains comprising Collaborative Cross (CC). We also performed whole-genome gene expression profiling in the retinae of all 8 strains using RNA-seq, and identified genes and pathways that correlated with refractive error and susceptibility to myopia.

Results : We found that C57BL/6J mice are essentially emmetropic (+0.3 ± 0.9 D). CAST/EiJ, NZO/HILtJ, PWK/PhJ, and WSB/EiJ mice exhibit various degrees of hyperopia ranging from +10.6±2.2 D to +22±4.0 D, whereas A/J, NOD/ShiLtJ, and 129S1/svlmj mice developed various degrees of myopia ranging from -3.5±3.6 D to -21.2±3.9 D. Analysis of the susceptibility to form-deprivation myopia in these 8 mouse strains revealed that genetic background also strongly influenced the extent of induced myopia. The myopic shift in refraction in the deprived eyes ranged from -5.6 ± 4.7 D to -20.0 ± 3.7 D. Gene expression profiling in the retina of 8 strains revealed that refractive error correlated with expression of 2,302 genes, whereas extent of induced myopia correlated with expression of 1,917 genes. 714 genes exhibited correlation with both refractive error and extent of myopia, and affected multiple signaling pathways. Additional analyses revealed that 92 genes, whose expression correlated with either refractive error and/or myopia, were localized within QTLs found to be linked to myopia in humans.

Conclusions : Our data suggest that genetic background influences both refractive eye development and susceptibility to myopia. We identified genes and signaling pathways underlying refractive development and susceptibility to myopia in mice. We also found a significant overlap between genes regulating refractive error development in mice and humans, thus, suggesting evolutionary conservation of signaling pathways underlying refractive eye development across vertebrate species as distant as mice and humans.

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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