title: Cfh genotype interacts with dietary glycemic index to modulate age-related macular degeneration-like features in mice.
abstract: OBJECTIVE
  Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide. Genetics and diet contribute to the relative risk for developing AMD, but their interactions are poorly understood. Genetic variations in Complement Factor H (CFH), and dietary glycemic index (GI) are major risk factors for AMD. We explored the effects of GI on development of early AMD-like features and changes to central nervous system (CNS) inflammation in Cfh-null mice.
  
  
  METHODS
  Aged 11-week-old wild type (WT) C57Bl/6J or Cfh-null mice were group pair-fed high or low GI diets for 33 weeks. At 10 months of age, mice were evaluated for early AMD-like features in the neural retina and RPE by light and electron microscopy. Brains were analyzed for Iba1 macrophage/microglia immunostaining, an indicator of inflammation.
  
  
  RESULTS
  The 10-month-old WT mice showed no retinal abnormalities on either diet. The Cfh-null mice, however, showed distinct early AMD-like features in the RPE when fed a low GI diet, including vacuolation, disruption of basal infoldings, and increased basal laminar deposits. The Cfh-null mice also showed thinning of the RPE, hypopigmentation, and increased numbers of Iba1-expressing macrophages in the brain, irrespective of diet.
  
  
  CONCLUSIONS
  The presence of early AMD-like features by 10 months of age in Cfh-null mice fed a low GI diet is surprising, given the apparent protection from the development of such features in aged WT mice or humans consuming lower GI diets. Our findings highlight the need to consider gene-diet interactions when developing animal models and therapeutic approaches to treat AMD.
authors.affiliation: JM-USDA Human Nutrition Research Center on Aging (HNRCA), Tufts University, Boston, Massachusetts.
authors.forename: Sheldon
authors.initials: S
authors.lastname: Rowan
authors.forename: Karen
authors.initials: K
authors.lastname: Weikel
authors.forename: Min-Lee
authors.initials: ML
authors.lastname: Chang
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Nagel
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Thinschmidt
authors.forename: Amanda
authors.initials: A
authors.lastname: Carey
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Fliesler
authors.forename: Donald
authors.initials: D
authors.lastname: Smith
authors.forename: Allen
authors.initials: A
authors.lastname: Taylor
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D017242:Complement Factor H / Q000235:genetics* / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004195:Disease Models, Animal; D005838:Genotype; D038321:Glycemic Index / Q000235:genetics*; D007150:Immunohistochemistry; D008268:Macular Degeneration / Q000178:diet therapy / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D055213:Retinal Pigment Epithelium / Q000648:ultrastructure
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D017242:Complement Factor H
keywords: aging; complement; gene-diet interaction; glycemic index; inflammation