June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Dietary Glycemia Contributes Reversibly to Age-related Macular Degeneration and Metabolic Disease in Aged C57Bl/6J Mice
Author Affiliations & Notes
  • Sheldon Rowan
    Human Nutrition Research Center on Aging, Tufts University, Boston, MA
  • Shuhong Jiang
    Human Nutrition Research Center on Aging, Tufts University, Boston, MA
  • Min-Lee Chang
    Human Nutrition Research Center on Aging, Tufts University, Boston, MA
  • Christa Cassalman
    Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA
  • Christina McGuire
    Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA
  • James D Baleja
    Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA
  • Barbara A Nagel
    Pathology, Saint Louis University, St. Louis, MO
  • Steven J Fliesler
    Biochemistry and Ophthalmology, SUNY University at Buffalo and the SUNY Eye Institute, Buffalo, NY
    Research Service, Veterans Administration Western New York Healthcare System, Buffalo, NY
  • Donald Smith
    Human Nutrition Research Center on Aging, Tufts University, Boston, MA
  • Allen Taylor
    Human Nutrition Research Center on Aging, Tufts University, Boston, MA
  • Footnotes
    Commercial Relationships Sheldon Rowan, None; Shuhong Jiang, None; Min-Lee Chang, None; Christa Cassalman, None; Christina McGuire, None; James Baleja, None; Barbara Nagel, None; Steven Fliesler, None; Donald Smith, None; Allen Taylor, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2333. doi:
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      Sheldon Rowan, Shuhong Jiang, Min-Lee Chang, Christa Cassalman, Christina McGuire, James D Baleja, Barbara A Nagel, Steven J Fliesler, Donald Smith, Allen Taylor; Dietary Glycemia Contributes Reversibly to Age-related Macular Degeneration and Metabolic Disease in Aged C57Bl/6J Mice. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2333.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Consuming high glycemia diets is a risk factor for Age-related Macular Degeneration (AMD) in humans. In an effort to elucidate mechanisms by which lower glycemia diets provide health benefit, we sought to test in aging C57Bl/6J mice whether a high glycemic index (GI) diet would lead to AMD-like lesions and other metabolic changes, and if the damage is reversible with dietary change to a lower GI diet.

Methods: 1-year old mice were fed high or low GI diets for one year. A crossover group had their diets shifted from high to low GI at the mid-point. Retina pathology was assessed via funduscopy, histology, and electron microscopy. Metabolic parameters, metabolites, advanced glycation end-products, and microbiota were measured from plasma, urine, or feces.

Results: Mice fed a high GI diet developed obesity and insulin resistance, characterized by reduced glucose tolerance and increased levels of insulin. These metabolic effects were fully reversible with dietary change. Many metabolic pathways, including tyrosine, citrate, and ascorbate pathways, advanced glycation endproducts, and gut microbiota showed diet-associated changes. Eyes from high GI-fed mice showed loss of photoreceptor cells and retina pathology consistent with early AMD, particularly in the superior retina near the optic nerve head. Pathology was less prominent in mice in the low GI or crossover groups. The RPE of high GI-fed mice was thinner (by 15.7%) and hypopigmented (by 28.2%) relative to the low GI diet group, while the crossover and low GI groups were not significantly different. The RPE of high GI-fed mice also contained increased numbers of lipofuscin particles (1.65X), phagosomes (9.56X), and evidence of poorly degraded photoreceptor outer segments (4.13X) relative to the low GI group.

Conclusions: Chronic consumption of a high glycemia diet induces metabolic disease and AMD-like retinal degeneration, which can be reversed by lowering dietary glycemia. The reversibility of AMD-like lesions by lowering dietary glycemia suggests that diet should be a primary intervention in treatment of early AMD, which lacks otherwise effective pharmaceutical treatments.

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