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Jie Zhang, Kuiyi Xing, Ye-Shih Ho, Marjorie F. Lou; Age-dependent Morphological and Biochemical Changes in the Lenses Of Thioltransferase (TTase, Or Grx1) Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1548.
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© ARVO (1962-2015); The Authors (2016-present)
TTase is an important regulator for redox homeostasis in the lens. Previously we have found that mice with TTase gene knockout (TTase KO) showed a faster cataract development than the wild type (WT) during aging. The purpose of this study is to examine the status of protein-thiol mixed disulfides in the lenses of TTase KO and WT mice during age-related cataract development.
TTase KO and WT mice of matching age between 1-25 months were examined using slit lamp and the lens opacity was classified and graded by LOSII system. Protein-S-S-glutathione (PSSG) and protein-S-S-cysteine (PSSC) in the whole lens homogenate were quantified using Dionex analyzer. Glutathione (GSH) was quantified by DTNB colorimetric method.
Slit lamp examination showed an age-dependent nuclear cataract development in both eyes of the WT and KO mice. The onset of cataract was 4 months in KO mice and 8 months in WT mice. The opacity covered the whole lens by 20 months in both groups. The incident and progression of cataract were more profound in the KO mice with 26% of the eyes showed opacity (10/38), 79% (22/28) in 8 months and 100% (18/18) in 12 months while the WT group was 40% (8/20) in 8 months, 50% (16/32) in 12 months and 100% (12/12) in 20 months. PSSG showed progressive elevation in the ages of 2, 7, 12 and 20 months in the KO group from 0.09, 0.15, 0.31 to 0.48 nmole/gdrywt, respectively. The level of PSSG in the WT was similar in 2, 7 months, but was only 0.22, 0.26 nmole/gdrywt in the 12, 20 months, respectively. In contrast, both groups showed similar PSSC level, which was low at 2-12 months and doubled at 20 months. GSH loss was also similar in both groups during aging.
The results suggest that TTase KO accelerated age-related cataract development and the PSSG formation in these lenses appeared to link directly to lens opacity. These data strengthen our hypothesis that TTase plays an essential role in maintaining lens clarity.
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