Targeted deletion of the murine Lgr4 gene decreases lens epithelial cell resistance to oxidative stress and induces age-related cataract formation

• Published in: PloS one 2015-03, Vol.10 (3), p.e0119599-e0119599
• Main Authors: Zhu, Jun, Hou, Qiang, Dong, Xiang Da, Wang, Zhenlian, Chen, Xiaoyan, Zheng, Dandan, Zhou, Linglin, He, Chao, Liu, Mingyao, Tu, LiLi, Qu, Jia
• Format: Article
• Language: English
• Subjects: Age; Age of Onset; Aging; Animals; Anterior segment dysgenesis syndrome; Antioxidants; Antioxidants (Nutrients); Biopolymer denaturation; Cancer; Catalase; Cataract - genetics; Cataract - metabolism; Cataract - pathology; Cataracts; Cell growth; Clonal deletion; Denaturation; Disease Models, Animal; Down-Regulation; Enzymes; Epithelial cells; Epithelial Cells - metabolism; G proteins; Gene Deletion; Gene expression; Gene Expression Regulation, Enzymologic; Gene Targeting; Genetic Association Studies; Genotype; Hospitals; Laboratories; Lens, Crystalline - metabolism; Lenses; Leucine; Metastasis; Mice; Mice, Knockout; Optometry; Oxidation; Oxidation resistance; Oxidative Stress; Phenotype; Protein denaturation; Proteins; Real time; Receptors, G-Protein-Coupled - deficiency; Receptors, G-Protein-Coupled - genetics; Science; Signal transduction; Superoxide dismutase
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0119599

Oxidative stress contributes to the formation of cataracts. The leucine rich repeat containing G protein-coupled receptor 4 (LGR4, also known as GPR48), is important in many developmental processes. Since deletion of Lgr4 has previously been shown to lead to cataract formation in mice, we sought to determine the specific role that Lgr4 plays in the formation of cataracts. Initially, the lens opacities of Lgr4(-/-) mice at different ages without ocular anterior segment dysgenesis (ASD) were evaluated with slit-lamp biomicroscopy. Lenses from both Lgr4(-/-) and wild-type mice were subjected to oxidation induced protein denaturation to assess the ability of the lens to withstand oxidation. The expression of antioxidant enzymes was evaluated with real-time quantitative PCR. Phenotypically, Lgr4(-/-) mice showed earlier onset of lens opacification and higher incidence of cataract formation compared with wild-type mice of similar age. In addition, Lgr4(-/-) mice demonstrated increased sensitivity to environmental oxidative damage, as evidenced by altered protein expression. Real-time quantitative PCR showed that two prominent antioxidant defense enzymes, catalase (CAT) and superoxidase dismutase-1 (SOD1), were significantly decreased in the lens epithelial cells of Lgr4(-/-) mice. Our results suggest that the deletion of Lgr4 can lead to premature cataract formation, as well as progressive deterioration with aging. Oxidative stress and altered expression of several antioxidant defense enzymes contribute to the formation of cataracts.