Metabolic syndrome triggered by high-fructose diet favors choroidal neovascularization and impairs retinal light sensitivity in the rat

PLoS One. 2014 Nov 7;9(11):e112450. doi: 10.1371/journal.pone.0112450. eCollection 2014.


Diabetic retinopathy and age-related macular degeneration are the leading causes of blindness in Western populations. Although it is a matter of controversy, large-scale population-based studies have reported increased prevalence of age-related macular degeneration in patients with diabetes or diabetic retinopathy. We hypothesized that metabolic syndrome, one of the major risk factors for type 2 diabetes, would represent a favorable environment for the development of choroidal neovascularization, the main complication of age-related macular degeneration. The fructose-fed rat was used as a model for metabolic syndrome in which choroidal neovascularization was induced by laser photocoagulation. Male Brown Norway rats were fed for 1, 3, and 6 months with a standard equilibrated chow diet or a 60%-rich fructose diet (n = 24 per time point). The animals expectedly developed significant body adiposity (+17%), liver steatosis at 3 and 6 months, hyperleptinemia at 1 and 3 months (two-fold increase) and hyperinsulinemia at 3 and 6 months (up to two-fold increase), but remained normoglycemic and normolipemic. The fructose-fed animals exhibited partial loss of rod sensitivity to light stimulus and reduced amplitude of oscillatory potentials at 6 months. Fructose-fed rats developed significantly more choroidal neovascularization at 14 and 21 days post-laser photocoagulation after 1 and 3 months of diet compared to animals fed the control diet. These results were consistent with infiltration/activation of phagocytic cells and up-regulation of pro-angiogenic gene expression such as Vegf and Leptin in the retina. Our data therefore suggested that metabolic syndrome would exacerbate the development of choroidal neovascularization in our experimental model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Angiography / methods
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Choroidal Neovascularization / etiology*
  • Diet / adverse effects
  • Electroretinography / drug effects
  • Fatty Acids / metabolism
  • Fatty Liver / etiology
  • Fructose / administration & dosage
  • Gene Expression / drug effects
  • Humans
  • Insulinoma / etiology
  • Laser Coagulation / adverse effects
  • Male
  • Metabolic Syndrome / complications*
  • Metabolic Syndrome / etiology
  • Rats, Inbred BN
  • Retina / drug effects
  • Retina / metabolism
  • Retina / physiopathology*
  • Retinal Rod Photoreceptor Cells / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Visual Acuity*


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Fatty Acids
  • Fructose

Grants and funding

This work was supported by Laboratoires Horus Pharma (Saint Laurent du Var, France), INRA-AlimH, CNRS, Université de Bourgogne, Regional Council of Burgundy France (PARI Agrale 1), FEDER (European Funding for Regional Economic Development), and French Government grant managed by the French National Research Agency (ANR) under the “Investissements d'Avenir” program with reference ANR-11-LABX-0021-01-LipSTIC Labex. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.