June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Association of αA-N101D with Lens Membrane Leads to Cell Membrane Disorganization, Intracellular Ionic Imbalance and Cataract Development in Transgenic αAN101D Mice

Author Affiliations & Notes
  • Om P Srivastava
    Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Kiran Srivastava
    Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Roy Joseph
    Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Om Srivastava, None; Kiran Srivastava, None; Roy Joseph, None
  • Footnotes
    Support  EY-06400
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5300. doi:
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      Om P Srivastava, Kiran Srivastava, Roy Joseph; Association of αA-N101D with Lens Membrane Leads to Cell Membrane Disorganization, Intracellular Ionic Imbalance and Cataract Development in Transgenic αAN101D Mice

      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):5300.

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

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Abstract

Purpose : To determine the effects of a common PTM (deamidation N to D at position 101 of αA-crystallin) in a mouse model with the N101D transgene that exhibited age-related cataract at about 7-months of age.

Methods : The age-related changes in lenses the of CRYAAN101D mice were examined with specific emphasis on protein insolubilization, aAN101D association with the membrane, and phenotypic changes at cellular and membrane organization levels to elucidate their roles in cataract development.

Results : Compared to the lenses of CRYAAWT, the lenses of CRYAAN101D exhibited an increasing age-related protein insolublization beginning at about 4-month of age. The immunogold-labeling and electron microscopic studies, and determination of the association of the αAN101D and WTαA with lens membranes showed relatively greater association of αAN101D with the membrane, and this was confirmed on in vitro binding assay of recombinant αAN101D and WTαA with purified lens membrane. A relatively greater outer cortical fiber cells disorganization and membrane swelling were also observed in CRYAAN101D lenses. Additionally, the higher Ca2+ levels and about 75% reduction of Na,K-ATPase mRNA in cultured epithelial cells of CRYAAN101D relative those from CRYAAWT further suggested a potential loss of membrane integrity and ionic imbalance.

Conclusions : The results suggested that an increased association of aAN101D with the membrane leads to ionic imbalance, membrane swelling, fiber cell disorganization and cataract development.

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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