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Stefanie J. Kirwin, Jeffrey L. Edelman; Diabetes Associated Gene Changes In The Retina Of Normo-glycemic Streptozotocin Treated Rats. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3581.
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© ARVO (1962-2015); The Authors (2016-present)
In rats, streptozotocin (STZ) is used to selectively destroy β-cells in the pancreas leading to insulin deficiency that mimics Type I diabetes mellitus. Early STZ induced changes in the retina, either by off-target pharmacologic activity, toxicity, or secondary effect of cell death in the pancreas, have not been adequately explored. This study uses whole genome array technology to assess gene expression in rats which remain normo-glycemic compared to those developing hyperglycemia after STZ treatment.
Rats were injected with 65 mg/kg STZ or buffer and blood glucose levels were determined after 48h. A small number of animals did not exhibit increased blood glucose levels after STZ injection and these were designated normo-glycemic STZ treated. Normo- and hyperglycemic STZ injected animals as well as controls were sacrificed 7 days after injection, retinas isolated and whole genome microarray analysis performed. Gene expression changes in STZ treated hyperglycemic rats (diabetic animals) vs. buffer control animals were calculated and compared to STZ treated normo-glycemic rats (non-diabetic animals) vs. buffer controls. Significantly changed genes were further analyzed for overlap between the two groups and biological functions.
Seven days after STZ injection, 393 genes are significantly changed in diabetic animals compared to 289 genes in non-diabetic animals. Of these genes only 43 are significantly changed in both groups and pathway analysis of the non-overlapping genes showed that biological functions affected in the diabetic rats differ from those treated with STZ, but non-diabetic. Multiple of the 43 genes overlapping between the two groups are associated with diabetes mellitus in human patients.
The data suggests that diabetes associated genes changed in both the diabetic and non-diabetic groups are affected by hypoinsulinemia rather than increased glucose levels or off target activity of STZ.
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