title: Long-standing hyperglycemia in C57BL/6J mice does not affect retinal glutathione levels or endothelial/pericyte ratio in retinal capillaries.
abstract: Free radicals have been suggested to play a role in the development of diabetic retinopathy. The aim of the present study was to examine whether the metabolic perturbations caused by high-fat feeding of two strains of mice, the C57BL6/J mice and the NMRI mice, interfere with one of the free radical enzyme defense systems in the retina, i. e., glutathione (GSH), and whether morphological changes occur in the retinal vessels. C57BL/6J mice and NMRI mice were fed a high-fat diet (55%) for 18 months. High-fat fed mice of both strains developed overweight, hyperinsulinemia, and hyperlipidemia. In addition, the high-fat fed C57BL/6J mice also developed sustained hyperglycemia for at least 15 months. The C57BL/6J mice had lower retinal GSH levels than the NMRI mice, both when given a normal diet (29.6+/-1.2 vs. 37.1+/-1.4 nmol/mg protein; p<0.01) and when given a high-fat diet (27.0+/-1.6 vs. 34.7+/-2.6 nmol/mg protein; p<0.05). Despite the long-standing hyperglycemia, hyperinsulinemia and hyperlipidemia in the C57BL/6J mice, high-fat feeding did not cause any changes in the retinal tissue levels of GSH (27.0+/-1.6 vs. 29. 6+/-1.2 nmol/mg protein) or cysteine (7.61+/-0.63 vs. 6.80+/-0.59 nmol/mg protein). Similarly, high-fat feeding did not affect retinal GSH or cysteine levels in NMRI mice. No light microscopical retinal vessel changes were seen, either in C57BL/6J or in NMRI mice. The study therefore shows that long-standing metabolic perturbations induced by dietary obesity do not induce signs of retinopathy in two different strains of mice. Further studies are needed to explore whether this is explained by increased expression of protecting systems making these strains of mice resistant to effects of oxidative stress.
authors.affiliation: Department of Endocrinology, University Hospital MAS, SE-205 02, Malmö, Sweden. carl-david.agardh@endo.mas.lu.se
authors.forename: C D
authors.initials: CD
authors.lastname: Agardh
authors.forename: E
authors.initials: E
authors.lastname: Agardh
authors.forename: B
authors.initials: B
authors.lastname: Hultberg
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002196:Capillaries / Q000473:pathology*; D003545:Cysteine / Q000378:metabolism; D004041:Dietary Fats; D004730:Endothelium, Vascular / Q000473:pathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D020286:Pericytes / Q000473:pathology; D012160:Retina / Q000378:metabolism*; D012171:Retinal Vessels / Q000473:pathology*; D013045:Species Specificity
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005978:Glutathione; D003545:Cysteine