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Qiang Hou, Jun Zhu, Lili Tu; Targeted Deletion of the Murine GPR48 Gene Decreases Lens Epithelial cells Resistance to Oxidative Stress and Induces Age-Related Cataract Formation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1206.
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We and collaborators have shown GPR48 deletion can cause cataract in mice. In this study, we try to further investigate the related molecular mechanisms.
The lens opacity of GPR48 knockout mice without ocular anterior segment dysgenesis (ASD) were checked with Slit-Lamp Biomicroscopy at different ages. The effects of oxidative stress on the lens epithelium and the lens of these mice were determined. Age matched lens from both Gpr48-/- and wild-type mice were subjected to oxidative stress such as peroxidase and oxidation induced protein denaturation to assess the ability of the lens to withstand oxidation. The expression of the antioxidant enzymes was evaluated with real-time quantitative PCR.
Phenotypically, GPR48 knockout mice showed higher incidence of cataract formation compared with wild-type mice of similar age. Lens opacification occurs earlier and to a more severe degree in Gpr48-/- mice when compared with the wild-type. Furthermore, the age matched lens from knockout mice demonstrated increased sensitivity to environmental oxidative damage. The results of real-time quantitative PCR showed that the expression of catalase (CAT) and superoxidase dismutase-1 (SOD-1), two prominent antioxidant defense enzymes, were significantly decreased in the lens epithelial cells of GPR48-/- mice.
Our results indicate that the deletion of GPR48 can cause age-related cataracts by decreasing the resistance of lens epithelial cells to oxidative stress. Its mechanism may be related to altered expression of several antioxidant defense enzymes, and this will need to be investigated further.
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