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Expression patterning reveals retinal inflammation as a minor factor in experimental retinopathy of ZDF rats.

Wohlfart P, Lin J, Dietrich N, Kannt A, Elvert R, Herling AW, Hammes HP - Acta Diabetol (2014)

Bottom Line: At 8 months of age, animals had developed microvascular complications.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.

View Article: PubMed Central - PubMed

Affiliation: R&D Diabetes Division, Research and Translational Medicine, Sanofi, Industriepark Höchst, 65926, Frankfurt, Germany, paulus.wohlfart@sanofi.com.

ABSTRACT
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.

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Quantitative assessment of gene expression by microfluidic card PCR. Relative expression to the geometric mean of three housekeeping genes is given and categorized into high (a), medium (b), and low abundant (c) expression. Asterisk denotes P < 0.05
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Fig2: Quantitative assessment of gene expression by microfluidic card PCR. Relative expression to the geometric mean of three housekeeping genes is given and categorized into high (a), medium (b), and low abundant (c) expression. Asterisk denotes P < 0.05

Mentions: VEGFa, MIF, and HIF-1α were the most abundantly expressed genes in retinas from both obese and lean ZDF rats, but not differentially regulated (Fig. 2). bFGF (FGF2) and placental growth factor (PGF) were significantly expressed and up-regulated in diabetic animals (5.4X for bFGF and 2.6X for PGF). Specific adhesion molecules, ITGAM, ITGB2, and ICAM1, were found to be significantly up-regulated in the diabetic environment. Nearly all inflammatory genes in our set were either not expressed or expressed at very low abundance. A significant up-regulation on a very low expression level could be observed for Il-1ß, but not for TNFα and IL-6. Fig. 2


Expression patterning reveals retinal inflammation as a minor factor in experimental retinopathy of ZDF rats.

Wohlfart P, Lin J, Dietrich N, Kannt A, Elvert R, Herling AW, Hammes HP - Acta Diabetol (2014)

Quantitative assessment of gene expression by microfluidic card PCR. Relative expression to the geometric mean of three housekeeping genes is given and categorized into high (a), medium (b), and low abundant (c) expression. Asterisk denotes P < 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4127441&req=5

Fig2: Quantitative assessment of gene expression by microfluidic card PCR. Relative expression to the geometric mean of three housekeeping genes is given and categorized into high (a), medium (b), and low abundant (c) expression. Asterisk denotes P < 0.05
Mentions: VEGFa, MIF, and HIF-1α were the most abundantly expressed genes in retinas from both obese and lean ZDF rats, but not differentially regulated (Fig. 2). bFGF (FGF2) and placental growth factor (PGF) were significantly expressed and up-regulated in diabetic animals (5.4X for bFGF and 2.6X for PGF). Specific adhesion molecules, ITGAM, ITGB2, and ICAM1, were found to be significantly up-regulated in the diabetic environment. Nearly all inflammatory genes in our set were either not expressed or expressed at very low abundance. A significant up-regulation on a very low expression level could be observed for Il-1ß, but not for TNFα and IL-6. Fig. 2

Bottom Line: At 8 months of age, animals had developed microvascular complications.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.

View Article: PubMed Central - PubMed

Affiliation: R&D Diabetes Division, Research and Translational Medicine, Sanofi, Industriepark Höchst, 65926, Frankfurt, Germany, paulus.wohlfart@sanofi.com.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus