Expression patterning reveals retinal inflammation as a minor factor in experimental retinopathy of ZDF rats.
Obese Zucker diabetic fatty (ZDF) rats are used as a type-2 diabetes model for microvascular complications. In order to study retinopathy in this model, changes in retinal vasculature were analyzed by quantitative morphometry and related to retinal expression of 46 selected genes that were analyzed by microfluidic card PCR technology. At 3 months of age, obese animals had developed stable hyperglycemia (20.7 ± 1.3 mmol/L plasma glucose vs. 6.5 ± 0.1 mmol/L in lean). Hyperinsulinemia initially presented in obese rats at 2 months (10.5 ± 0.7 μg/L plasma insulin vs. 0.2 ± 0.04 μg/L in lean) and decreased at 3 months (3.9 ± 0.6 vs. 0.5 ± 0.09 μg/ml in lean). At 8 months of age, animals had developed microvascular complications. An increased number of acellular capillaries in obese (24 ± 5/mm(2)) versus lean (15 ± 4/mm(2)) and a decreased number of retinal pericytes in obese (2,270 ± 250/mm(2)) versus lean animals (1,620 ± 243/mm(2)) could be observed. VEGFa, MIF, and HIF-1α were the most abundantly expressed and inflammatory genes such as TNFα and IL-6 are the least abundantly expressed genes. None of these genes were differentially regulated. Surprisingly, specific growth factors such as bFGF (FGF2) and placental growth factor, and adhesion molecules such as ICAM-1 were abundantly expressed and up-regulated in diabetic versus non-diabetic ZDF rats. In summary, we observed in type-2 diabetic ZDF rats retinopathy with retinal vasoregression along with a simultaneous up-regulation of specific growth factors such as bFGF and adhesion molecules, but only minor changes in key inflammatory genes.
R&D Diabetes Division, Research and Translational Medicine, Sanofi, Industriepark Höchst, 65926, Frankfurt, Germany, paulus.wohlfart@sanofi.com.
Paulus
P
Wohlfart
Jihong
J
Lin
Nadine
N
Dietrich
Aimo
A
Kannt
Ralf
R
Elvert
Andreas W
AW
Herling
Hans-Peter
HP
Hammes
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003930:Diabetic Retinopathy / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008297:Male; D051381:Rats; D011924:Rats, Zucker; D012160:Retina / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2