Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #307544
Title: Cfh genotype interacts with dietary glycemic index to modulate age-related macular degeneration-like features in mice

Author
item ROWAN, SHELDON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item WEIKEL, KAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item CHANG, MIN-LEE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item NAGEL, BARBARA - St Louis University
item THINSCHMIDT, JEFFERY - University Of Florida
item CAREY, AMANDA - Simmons College
item GRANT, MARIA - University Of Florida
item FLIESLER, STEVEN - State University Of New York (SUNY)
item SMITH, DONALD - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item TAYLOR, ALLEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Investigative Ophthalmology and Visual Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/22/2013
Publication Date: 1/23/2014
Citation: Rowan, S., Weikel, K., Chang, M., Nagel, B.A., Thinschmidt, J.S., Carey, A., Grant, M.B., Fliesler, S.J., Smith, D., Taylor, A. 2014. Cfh genotype interacts with dietary glycemic index to modulate age-related macular degeneration-like features in mice. Investigative Ophthalmology and Visual Science. 55(1):492-501.

Interpretive Summary: Age-related Macular Degeneration (AMD) is the leading cause of blindness in the United States and affects millions of people. It is caused by the death of light sensing cells in the part of our eye that we use for most of our central color vision. While there are disease contributions from our genes, environment, age, and diet, it is easier to change diet than other factors. We know from clinical studies in humans and experimental studies in mice that the kinds of foods in the diet are important in disease risk for AMD; foods that break down rapidly into sugar are worse for you than foods that take longer to break down into sugar – this is known as the glycemic index. We also know from clinical studies that constant exposure to inflammation can contribute to AMD. We used mice that were genetically engineered to have high amounts of inflammation and wanted to know whether they would get an AMD-like disease with aging if we fed them diets high or low in the glycemic index. We expected that mice fed a high glycemic index diet would be more affected, but instead saw the opposite result; mice fed a low glycemic index diet developed AMD-like disease, but only the high inflammation mice and not regular mice. We examined other tissues in the mice and found that the high inflammation mice did have higher amounts of inflammation in their brains and that the diet didn’t appear to matter for inflammation. What our experiments taught us is that neither genes nor diet work alone, but they impact each other in unpredictable ways. This has real-life implications in thinking about what the right dietary changes are for a given person. We believe that some individuals are genetically programmed to respond better to one diet than another and if we could take advantage of that knowledge, could tailor better preventive and/or treatments for diseases like AMD.

Technical Abstract: 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. 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. 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. 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.