May 2005
Volume 46, Issue 13
ARVO Annual Meeting Abstract  |   May 2005
Age–Related Cataract in Anti–Oxidant Altered Mice
Author Affiliations & Notes
  • N.S. Wolf
    Pathology, Univ. Washington, Seattle, WA
  • W. Pendergrass
    Pathology, Univ. Washington, Seattle, WA
  • H. VanRemmen
    Cellular and Structural Biology, Universit of Texas Health Sciences at San Antonio, San Antonio, TX
  • A. Bartke
    Department of Medicine, Southern Illinois University, Springfield, IL
  • P. Rabinovitch
    Pathology, Univ. Washington, Seattle, WA
  • G.M. Martin
    Pathology, Univ. Washington, Seattle, WA
  • Footnotes
    Commercial Relationships  N.S. Wolf, None; W. Pendergrass, None; H. VanRemmen, None; A. Bartke, None; P. Rabinovitch, None; G.M. Martin, None.
  • Footnotes
    Support  NIH Grant EY11733
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 2904. doi:
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      N.S. Wolf, W. Pendergrass, H. VanRemmen, A. Bartke, P. Rabinovitch, G.M. Martin; Age–Related Cataract in Anti–Oxidant Altered Mice . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2904.

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

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Abstract: : Purpose:To examine the effect on age–related cataract of removing or diminishing, versus increasing, specific anti–oxidant enzymes or homonal stimulation in the lens. Methods: In separate groups mice were deprived homozygously of GPX1, or heterozygously of SOD1, or both, by homologous recombination knockouts, or had additional catalase added only to the mitochondria by targeted transcarbamylase leader sequence. All mice were then bred back at least 10 generations onto the C57BL/6 strain background. In addition, mice on an outbred mixed background with knockout of the growth hormone receptor (GHRKO) and no circulating IGF1 were separately prepared. The mice were then examined at 4–5 months or 21–30 months by hand held slit lamp use by a single blinded observer. Cataracts were graded progressively as 0 to4+, with the latter representing a mature cataract. Results: Mutant mice with no GPX1 developed graded cataracts that were significantly advanced over that of controls in late life; Mice with 50% of normal levels of SOD2 did not differ from controls; mice bearing both deletions developed cataracts with the same age–related advancement as the GPX1 KO mice alone, with no added effect from the half–reduced SOD2. Mice with catalase added only to the mitochondria showed a significant delay in cataract development at 15–17 months of age, but this advantage was reduced to p=.06 by 24 months and lost entirely by 30 months. Mice with knockout of the GH receptor (GHRKO) had significantly less advanced cataracts in old age. Conclusions: These findings provide support for the oxidative causality of age–related cataract development, with the notable exception of the SOD2 heterozygous KO mutant. It is noted that 50% of the normal level of SOD2 may be sufficient to provide the adequate activity of SOD2, i.e., the conversion of O* to H202 in the lens. The cataract delay in the GHRKO mice are an example of the protection from oxidative damage provided by the removal of circulating IGF1, as has been seen in other studies testing tissues and the whole mouse against oxidative challenges. These studies empasize the interplay of specfic genes and the environment in the development of age–related cataract.

Keywords: cataract • cataract • gene/expression 

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