Effect of Methyl-CpG Binding Domain Protein 2(MBD2) on AMD-like Lesions in ApoE-Deficient Mice  

作　　者：潘俊如 王琛 余其林 张述 李斌 胡军 

机构地区：[1]Department of Ophthalmology,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2]The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

出　　处：《Journal of Huazhong University of Science and Technology(Medical Sciences)》2014年第3期408-414,共7页华中科技大学学报（医学英德文版）

基　　金：supported by grants from Natural Science Foundation of Hubei Province(No:2012FFB02304);Scientific Research Foundation of Ministry of Education(No:2013-1792),China

摘　　要：Summary： The role of methyl-CpG binding domain protein 2 （MBD2） in an ApoE-deficient mouse model of age-related macular degeneration （AMD） was investigated. Eight-week-old Mbd2/ApoE double deficient （Mbd2^-/- ApoE^-/-） mice （n=12, 24 eyes, experimental group） and MBD2 （wt） ApoE^-/- mice （n=12, 24 eyes, control group） were fed on Western-type diet for 4 months. The mice were sacrificed, and total serum cholesterol levels were analyzed and Bruch＇s membrane （BM） of the eyes was removed for ultrastructural observation by transmission electron microscopy. Moreover, intercellular adhesion molecule 1 （ICAM-1） immunoreactivities were evaluated by fluorescence microscopy in sections of the eyes in both groups for further understanding the function mechanism of MBD2. There was no significant difference in the total serum cholesterol levels between control group and experimental group （P〉0.05）. Transmission electron microscopy revealed that AMD-like lesions, various vacuoles accumulated on BM, notable outer collagenous layer deposits and dilated basal infoldings of retinal pigment epithelium （RPE） were seen in both groups, and the BM in control group was significantly thickened as compared with experimental group （P〈0.05）. Fluorescence micrographs exhibited the expression of ICAM-1 in choroid was higher in control group than in experimental group. We are led to conclude that MBD2 gene knockout may lead to accumulation of more deposits on the BM and influence the pathogenesis of AMD via triggering endothelial activation and inflammatory response in choroid, improving microcirculation, and reducing lipid deposition so as to inhibit the development of AMD-like lesions. Our study helps to provide a new therapeutic approach for the clinical treatment of AMD.Summary： The role of methyl-CpG binding domain protein 2 （MBD2） in an ApoE-deficient mouse model of age-related macular degeneration （AMD） was investigated. Eight-week-old Mbd2/ApoE double deficient （Mbd2^-/- ApoE^-/-） mice （n=12, 24 eyes, experimental group） and MBD2 （wt） ApoE^-/- mice （n=12, 24 eyes, control group） were fed on Western-type diet for 4 months. The mice were sacrificed, and total serum cholesterol levels were analyzed and Bruch＇s membrane （BM） of the eyes was removed for ultrastructural observation by transmission electron microscopy. Moreover, intercellular adhesion molecule 1 （ICAM-1） immunoreactivities were evaluated by fluorescence microscopy in sections of the eyes in both groups for further understanding the function mechanism of MBD2. There was no significant difference in the total serum cholesterol levels between control group and experimental group （P〉0.05）. Transmission electron microscopy revealed that AMD-like lesions, various vacuoles accumulated on BM, notable outer collagenous layer deposits and dilated basal infoldings of retinal pigment epithelium （RPE） were seen in both groups, and the BM in control group was significantly thickened as compared with experimental group （P〈0.05）. Fluorescence micrographs exhibited the expression of ICAM-1 in choroid was higher in control group than in experimental group. We are led to conclude that MBD2 gene knockout may lead to accumulation of more deposits on the BM and influence the pathogenesis of AMD via triggering endothelial activation and inflammatory response in choroid, improving microcirculation, and reducing lipid deposition so as to inhibit the development of AMD-like lesions. Our study helps to provide a new therapeutic approach for the clinical treatment of AMD.

关 键 词：methyl-CpG binding domain protein 2 aged-related macular degeneration endothelial dysfunction intercellular adhesion molecule 1 

分 类 号：R774.5[医药卫生—眼科]