May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Oxidative Damage to Connexins Precedes Cataract Formation in Lenses From Glutathione Peroxidase–1 Deficient Mice
Author Affiliations & Notes
  • H. Wang
    Physiology & Biophysics, SUNY at Stony Brook, Stony Brook, NY
  • F.J. Martinez–Wittinghan
    Physiology & Biophysics, SUNY at Stony Brook, Stony Brook, NY
  • X. Sun
    Physiology & Biophysics, SUNY at Stony Brook, Stony Brook, NY
  • J. Gao
    Physiology & Biophysics, SUNY at Stony Brook, Stony Brook, NY
  • K. Varadaraj
    Physiology & Biophysics, SUNY at Stony Brook, Stony Brook, NY
  • V.N. Reddy
    Kellogg Eye Center, Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI
    Eye Research Institute, Oakland University, Rochester, MI
  • R.T. Mathias
    Physiology & Biophysics, SUNY at Stony Brook, Stony Brook, NY
  • Footnotes
    Commercial Relationships  H. Wang, None; F.J. Martinez–Wittinghan, None; X. Sun, None; J. Gao, None; K. Varadaraj, None; V.N. Reddy, None; R.T. Mathias, None.
  • Footnotes
    Support  NIH Grants: EY06391, EY00484
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 1852. doi:
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      H. Wang, F.J. Martinez–Wittinghan, X. Sun, J. Gao, K. Varadaraj, V.N. Reddy, R.T. Mathias; Oxidative Damage to Connexins Precedes Cataract Formation in Lenses From Glutathione Peroxidase–1 Deficient Mice . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1852.

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

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Abstract

Abstract: : Purpose: A recent study of lenses from glutathione peroxidase–1 knockout mice (GPX–/–) revealed age related oxidative damage to fiber cell membranes and crystallins, resulting in a nuclear cataract. We have looked at membrane transport properties of GPX–/– lenses at an early age to see if we could detect changes that precede the cataract. Methods: Intact lenses were characterized using impedance studies. Isolated epithelial cells were studied using whole cell patch clamp to determined Na/K pump current (IP). Impedance studies were performed on freshly dissected lenses from wild type and GPX–/– mice (6–8 weeks old), and guinea pig lenses cultured for 5 days in control or elevated (100 µM) H2O2 solutions. IP was measured in equatorial epithelial cells isolated from guinea pig lenses; we were unable to study IP in mouse lens epithelial cells. Results: GPX–/– lenses did not have any obvious reduction in transparency at this age, and their membrane conductances as well as resting voltage were not different from wild type. However, they had significantly reduced coupling conductance in both peripheral differentiating fibers (DF) and central mature fibers (MF): GDF(WT)=0.81±0.07, n=23, GDF(GPX–/–)=0.60±0.09, n=8; GMF (WT)=0.43±0.08, n=28, GMF(GPX–/–)=0.19±0.03, n=8 (S/cm2). Although coupling conductance was reduced in the GPX–/– lenses, it had the same pH sensitivity as WT. H2O2 cultured guinea pig lenses did not have significant differences in coupling conductance when compared with control, however they had significantly reduced IP: IP(Con)=0.31±0.04, n=8; IP(H2O2)= 0.19±0.06, n=9 (pA/pF). Conclusions: Short term oxidative stress caused a reduction in Na/K pump activity but did not affect gap junctional coupling. However, long term oxidative stress reduced coupling conductance well before cataract formation. Furthermore, the changes in coupling were similar to those produced by knocking out one Cx46 allele. Thus age related cataract could be the consequence of oxidative damage to Cx46 and compromise of the lens circulatory system. Although IP was not measured in the GPX–/– lenses, if it were also compromised, as in the guinea pig lenses, this would further compromise the lens circulation.

Keywords: gap junctions/coupling • oxidation/oxidative or free radical damage • transgenics/knock-outs 
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