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S. J. Kirwin, J. L. Edelman; Strain-Specific Changes in Gene Expression in Retinae From Streptozotocin-Treated Diabetic Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1328. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy is a common complication of human diabetes for which streptozotocin (STZ) induced hyperglycemia in rats is an accepted animal model. However, there is little data to document how the response to excessive glucose in the retina differs between rat strains. In order to determine the extent of differences between three commonly used rat strains, changes in gene expression in the retina of diabetic Sprague Dawley (SD), Brown Norway (BN), and Long Evans (LE) rats were compared using whole genome microarray analysis through three months after the induction of diabetes.
Male SD, BN, and LE rats were rendered diabetic by intraperitoneal STZ (65 mg/kg; blood glucose >220 mg/dl after 48h), and age-matched control rats were sacrificed at 7 days, 4 weeks, and 3 months. Eyes were enucleated, dissected in ice-cold saline and retinae transferred to RNAlater. Whole rat genome analysis was performed by Genus Biosystems using Agilent Array Technology.
Analysis of changes in gene expression in three rat strains seven days after induction of diabetes revealed strain-dependent responses to hyperglycemia. Although the number of genes changed more then 1.5-fold was similar between the strains, no single gene was significantly up- or down-regulated in all three. Furthermore, pathway analysis showed distinct biological responses between the groups. Gene expression also varied widely between strains at 4 weeks, and though the ratio of up- and down-regulated genes was similar between BN and LE rats, there was a marked increase in the number of down-regulated genes in SD rats. Similar to the 1 week time point, there were no overlapping pathways. Although preliminary data show potentially more overlap in the expression of individual genes at 3 months, the vast majority of genes differentially expressed suggest an equally varied response between the strains at this late time point.
These data show that hyperglycemia induces diverse transcriptional responses in the retina of three rat strains commonly used to study diabetic retinopathy, and this finding may explain some of the variability from published results using this model. Analysis of different pathways utilized by each strain may serve as a guideline in strain selection for further studies.
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