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Yibo Yu, Hongli Wu, Ye-Shih Ho, Marjorie F. Lou; Glutaredoxin 2 (Grx2) Gene Knockout Accelerates Age-Related Cataract Development in Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2084.
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Glutaredoxin 2 (Grx2) is an isozyme of thioltransferase (TTase or Grx1) and present in the mitochondria where it may protect the organnell from oxidative damage and regulate its redox balances. However, Grx2 function is largely unknown. We recently developed a Grx2 knockout (KO) mouse model in which the primarylens epithelial cells have demonstrated a strong sensitivity to H2O2-induced cell injury. The purpose of this study is to investigate if Grx2 KO model shows a phenotype of early age-related cataract development in vivo.
Slit lamp was used to examine the lenses in Grx2 null mice (26) and age-matched wild-type (WT) mice (26) ranging from 2 to 11 months. Cataract classification and grading (score) used LOCS II system and the sum of the scores from nucleus (N), cortex (C) and posterior sub-capsular (P) opacity were used to analyze the severity of cataract.
Grx2 null mice showed normal development with similar body weight and function as the WT mice of the same background. Slit lamp examination found mostly nuclear cataract in both WT and Grx2 KO mice. The lenses in WT were clear during the first 6 months but light nuclear opacity appeared at 8 months in 2 of the 10 eyes (rate 20%, 2/10), and by 11 months the rate reached 30% (3/10). However, in Grx2 null mice, nuclear opacity was found at 4 months in one of the 10 eyes (1/10). The rate of cataract formation was accelerated to 25% (2/8) at 6 months, 40% (4/10) at 8 months, and 92% (11/12) at 11 months. In both groups the lens opacity remained relatively light with score of 1 (C0N1P0). The rate of cataract formation between the two groups at 11 months was significant (P<0.05).
Cataract development in Grx2 null mice appeared to progress from nuclear opacities, and the opacity formed at an earlier age with a higher incidence than that of the age-matched WT mice. The results suggest that Grx2 plays a key role in maintaining lens transparency.
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