June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Multiple abnormalities precede cataracts in Cx46fs380 mice
Author Affiliations & Notes
  • Eric C Beyer
    Pediatrics, University of Chicago, Chicago, Illinois, United States
  • Junyuan Gao
    Physiology and Biophysics, Stony Brook University, Stony Brook, New York, United States
  • Peter J. Minogue
    Pediatrics, University of Chicago, Chicago, Illinois, United States
  • Layne A. Novak
    Illinois College of Optometry, Chicago, Illinois, United States
  • Rebecca K Zoltoski
    Illinois College of Optometry, Chicago, Illinois, United States
  • Richard T Mathias
    Physiology and Biophysics, Stony Brook University, Stony Brook, New York, United States
  • Viviana M Berthoud
    Pediatrics, University of Chicago, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Eric Beyer, None; Junyuan Gao, None; Peter Minogue, None; Layne Novak, None; Rebecca Zoltoski, None; Richard Mathias, None; Viviana Berthoud, None
  • Footnotes
    Support  NIH R01 EY08368
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2472. doi:
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    • Get Citation

      Eric C Beyer, Junyuan Gao, Peter J. Minogue, Layne A. Novak, Rebecca K Zoltoski, Richard T Mathias, Viviana M Berthoud; Multiple abnormalities precede cataracts in Cx46fs380 mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2472.

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

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Abstract

Purpose : Cx46fs380 mice model a human congenital autosomal-dominant cataract caused by a mutant lens connexin, Cx46. The present studies were conducted to determine whether there are lens abnormalities in these mice before there are detectable cataracts. In homozygous Cx46fs380 mice, cataracts are first observed around 2 months of age, while in heterozygotes, they are not seen until 4 months of age or later.

Methods : Lenses from wild type mice and Cx46fs380 heterozygotes and homozygotes were studied at 1-3 months of age to determine refractive properties (by photographing the lenses above a 200-mesh electron microscopy grid), focusing ability (by laser scanning), and membrane potential, gap junctional coupling and hydrostatic pressure (by microelectrode studies of intact lenses).

Results : Lenses from homozygous mice significantly distorted the EM grid pattern and had reduced focal lengths compared to wild type lenses. The differentiating and mature fiber cells of heterozygous and homozygous Cx46fs380 animals had significantly depolarized membrane potentials; this alteration was more severe in homozygotes. Gap junctional coupling was decreased in both mature and differentiating fibers in heterozygous and homozygous Cx46fs380 mice; in homozygotes, the mature fibers had no detectable coupling. Hydrostatic pressure was also significantly increased in the lenses of mutant mice (homozygotes > heterozygotes).

Conclusions : Homozygous Cx46fs380 mice have alterations of lens refractive and focusing properties that are detectable before the appearance of cataracts and are consistent with myopia. Changes in membrane potential, gap junctional conductance, and hydrostatic pressure are present in all mutant lenses and precede cataract formation (at least in heterozygotes). Taken together, these data suggest that expression of Cx46fs380 causes a series of events affecting lens electrophysiological parameters, water flow, and optical properties prior to development of visible opacities.

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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