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J. L. Edelman, S. J. Kirwin; Hyperglycemia-Induced Inflammatory Protein and Growth Factor Expression in Retina From Three Rat Strains. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4911.
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© ARVO (1962-2015); The Authors (2016-present)
Streptozotocin (STZ)-induced diabetes in rats is an established animal model for complications of human diabetes, including diabetic retinopathy. There is evidence suggesting a role for inflammation in this disease. In order to assess the severity of inflammation in this model, and to identify potential rat strain-specific responses, retinal levels of sixty-eight cytokines, growth, factors, and hematological proteins were tested in three rat strains after inducing hyperglycemia with STZ.
Male Sprague Dawley, Brown Norway, and Long Evans rats were rendered diabetic by intraperitoneal STZ administration (65 mg/kg; blood glucose >220 mg/dl after 48h) and age-matched control rats were sacrificed 7 days and 4 weeks after STZ injection. Eyes were enucleated, snap frozen in liquid nitrogen and stored at -70°C. Protein was extracted by tissue sonication in TrisHCl pH 7.5 and analyzed by Rules Based Medicine (Austin, TX) using the RodentMAPTM Antigen panel.
Of the 68 proteins quantified, similar expression patterns were observed in normal and diabetic retinas in the three rat strains. Several important inflammatory molecules were not detected in diabetic or control retinas at 7 days or 4 weeks after induction of diabetes, including (but not limited to) interleukin (IL)-1β, IL-6, IL-12, IL-18, interferon-γ, RANTES, tumor necrosis factor α, and vascular cell adhesion molecule-1. A number of proteins are expressed in both control and diabetic retina that are not regulated by hyperglycemia including endothelin-1, bFGF, C reactive protein, TIMP-1, IL-2, calbindin, and fibrinogen. In contrast, hyperglycemia induces the upregulation of the inflammatory cytokines IL-1α, NGAL, and eotaxin, as well as fibroblast growth factor (FGF)-9 and myoglobin by 4 weeks. At this time, there is also a small, but reproducible increase in vascular endothelial growth factor (VEGF) in diabetic retinas.
The results of this study show that multiple inflammatory and angiogenic proteins are upregulated in retina through one month of hyperglycemia. Diabetes-induced changes in protein expression are strain independent, and these results support the hypothesis that the early stages of this disease are associated with a subclinical inflammatory response.
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