title: Effect of Methyl-CpG binding domain protein 2 (MBD2) on AMD-like lesions in ApoE-deficient mice.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Huazhong University of Science and Technology, Wuhan, 430030, China.|The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jun-Ru
authors.initials: JR
authors.lastname: Pan
authors.affiliation: Department of Ophthalmology, Huazhong University of Science and Technology, Wuhan, 430030, China.|The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qi-Lin
authors.initials: QL
authors.lastname: Yu
authors.affiliation: The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Huazhong University of Science and Technology, Wuhan, 430030, China. hu-jun525@hotmail.com.|The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. hu-jun525@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D016570:Bruch Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002784:Cholesterol / Q000097:blood; D002829:Choroid / Q000378:metabolism / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008268:Macular Degeneration / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D001057:Apolipoproteins E; D004268:DNA-Binding Proteins; C489326:Mbd2 protein, mouse; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol