Cfh genotype interacts with dietary glycemic index to modulate age-related macular degeneration-like features in mice

Sheldon Rowan, Karen Weikel, Min Lee Chang, Barbara A. Nagel, Jeffrey S. Thinschmidt, Amanda Carey, Maria B. Grant, Steven J. Fliesler, Donald Smith, Allen Taylor

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

PURPOSE. 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 AMDlike 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 Cfhnull 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.

Original languageEnglish (US)
Pages (from-to)492-501
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number1
DOIs
StatePublished - Dec 26 2013

Keywords

  • Aging
  • Complement
  • Gene-diet interaction
  • Glycemic index
  • Inflammation

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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