Investigative Ophthalmology & Visual Science Cover Image for Volume 57, Issue 12
September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Eliminating the Master Clock Gene in the Murine Retina Produces Myopia
Author Affiliations & Notes
  • Duk Cheon Lee
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA center, Decatur, Georgia, United States
  • Ranjay Chakraborty
    Ophthalmology, Emory University, Atlanta, Georgia, United States
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA center, Decatur, Georgia, United States
  • P. Michael Iuvone
    Ophthalmology, Emory University, Atlanta, Georgia, United States
    Pharmacology, Emory University, Atlanta, Georgia, United States
  • Richard A Stone
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Machelle T Pardue
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA center, Decatur, Georgia, United States
    Biomedical Engineering, Georgia Institue of Technology / Emory University, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Duk Cheon Lee, None; Ranjay Chakraborty, None; P. Michael Iuvone, None; Richard Stone, None; Machelle Pardue, None
  • Footnotes
    Support  NEI Grants EY022342, EY004864, EY016435, NIH Core grant P30EY006360, Research to Prevent Blindness Grants to Emory and Penn, Department of Veterans Affairs Research Career Scientist Award (MTP) and the Mackall Foundation Trust (RAS).
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3616. doi:
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    • Get Citation

      Duk Cheon Lee, Ranjay Chakraborty, P. Michael Iuvone, Richard A Stone, Machelle T Pardue; Eliminating the Master Clock Gene in the Murine Retina Produces Myopia. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3616.

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

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Abstract

Purpose : BMAL1 is a transcription factor that is essential to the operation of the circadian clock mechanism in all tissues of the body, including the retina. Previous studies with chicks have linked intrinsic retinal circadian rhythms to experimental myopia (Stone et al., 2013). In this study, Cre-mediated, retinal specific BMAL1 knockout (KO) mice were examined to determine whether the BMAL1 gene and, by inference, circadian rhythms have a role in normal refractive development of the eye.

Methods : KO mice were on a C57BL/6J background and were homozygous for both the Chx10 Cre-recombinase and floxed Bmal1 alleles. Refractive development of KO (n=7) and age-matched wild-type (WT, n=10) mice were measured every 2 weeks from post-natal day 28 (P28) to P112 under normal laboratory visual conditions. Measurements of refractive error, corneal radius of curvature, and ocular biometric parameters were collected using an automated photorefactor, keratometer, and spectral-domain optical coherence tomography (SD-OCT) system, respectively.

Results : Under normal visual conditions, KO mice were significantly more myopic than WT mice throughout the developmental period (at P70: KO -0.413 ± 0.80 D; WT +4.81 ± 0.90 D; p<0.001). KO mice had longer axial lengths than WT mice (at P70: KO +3.24 ± 0.02 mm; WT +3.21 ± 0.01 mm; p=0.007). KO mice also showed shorter anterior chamber depths (at P70: KO +0.37 ± 0.003 mm; WT +0.38 ± 0.002 mm; p=0.01) and longer vitreous chambers (at P70: KO +0.61 ± 0.003 mm; WT +0.57 ± 0.002mm; p<0.001) than the WT mice. There were no significant differences in corneal curvature between KO and WT animals.

Conclusions : Our results indicate that Bmal1 is important for normal refractive development of the eye in mice. Future studies are needed to examine underlying mechanisms causing myopic refractive errors in Bmal1 KO mice and to evaluate the response of Bmal1 KO mice to modified visual input.

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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