Metabolic syndrome triggered by high-fructose diet favors choroidal neovascularization and impairs retinal light sensitivity in the rat.
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.
INRA, UMR 1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, Dijon, France; CNRS, UMR 6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
Magalie
M
Thierry
INRA, UMR 1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, Dijon, France; CNRS, UMR 6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
Bruno
B
Pasquis
INRA, UMR 1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, Dijon, France; CNRS, UMR 6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
Niyazi
N
Acar
INRA, UMR 1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, Dijon, France; CNRS, UMR 6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
Stéphane
S
Grégoire
INRA, UMR 1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, Dijon, France; CNRS, UMR 6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
Valérie
V
Febvret
INRA, UMR 1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, Dijon, France; CNRS, UMR 6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
Bénédicte
B
Buteau
INRA, UMR 1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, Dijon, France; CNRS, UMR 6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Department of Clinical Chemistry, University Hospital, Dijon, France.
Ségolène
S
Gambert-Nicot
INRA, UMR 1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, Dijon, France; CNRS, UMR 6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Department of Ophthalmology, University Hospital, Dijon, France.
Alain M
AM
Bron
INRA, UMR 1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, Dijon, France; CNRS, UMR 6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Department of Ophthalmology, University Hospital, Dijon, France.
Catherine P
CP
Creuzot-Garcher
INRA, UMR 1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, Dijon, France; CNRS, UMR 6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
Lionel
L
Bretillon
D000273:Adipose Tissue / Q000378:metabolism; D000792:Angiography / Q000379:methods; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000209:etiology*; D004032:Diet / Q000009:adverse effects; D004596:Electroretinography / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology; D005632:Fructose / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007340:Insulinoma / Q000209:etiology; D017075:Laser Coagulation / Q000009:adverse effects; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000209:etiology; D011914:Rats, Inbred BN; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014792:Visual Acuity; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005227:Fatty Acids; D005632:Fructose; C067980:CD68 antigen, human; D000097382:CD68 Molecule