title: Effects of simvastatin on retinal structure and function of a high-fat atherogenic mouse model of thickened Bruch's membrane.
abstract: OBJECTIVE
  To determine the effect of a statin (simvastatin) on the ultrastructure and function of the RPE, Bruch's membrane (BM), and photoreceptor interface in a high-fat atherogenic mouse model of thickened BM.
  
  
  METHODS
  Wild-type C57BL/6 mice (6-weeks old) were divided into three study groups according to their diet and treatment given; Group 1, normal chow diet-fed mice; Group 2, high fat diet (HFD) fed mice; and Group 3, HFD-fed mice treated with simvastatin daily for 30 weeks. All mice were followed-up for 30 weeks. The retinal morphology and function was examined in vivo using fundus imaging and electroretinography at 15- and 30-weeks follow-up. At the end of the study, at 36 weeks of age, eye tissues were collected and retinal sections were examined using light microscopy and transmission electron microscopy.
  
  
  RESULTS
  Fundus images of the HFD-fed mice showed the presence of discrete, multiple white spots, which was significantly reduced by approximately 73% in the simvastatin-treated animals. In the HFD-fed mice, there was an increase in the empty cytoplasmic vacuoles of the RPE, presence of lipid droplets in the BM, thickening and fragmentation of the elastic lamina of the BM, and a reduction in retinal function; these ultrastructural and functional changes were significantly improved in the simvastatin-treated group.
  
  
  CONCLUSIONS
  Chronic administration of simvastatin significantly improves the ultrastructure and function of the RPE, BM, and photoreceptor in a high-fat atherogenic mouse model of thickened BM.
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Veluchamy A
authors.initials: VA
authors.lastname: Barathi
authors.forename: Sia W
authors.initials: SW
authors.lastname: Yeo
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Guymer
authors.forename: Tien Y
authors.initials: TY
authors.lastname: Wong
authors.forename: Chi D
authors.initials: CD
authors.lastname: Luu
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016570:Bruch Membrane / Q000187:drug effects / Q000648:ultrastructure*; D004195:Disease Models, Animal; D004596:Electroretinography; D005500:Follow-Up Studies; D008268:Macular Degeneration / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure*; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D019821:Simvastatin
keywords: Bruch's membrane; electroretinography; high-fat atherogenic mouse model; retina; simvastatin