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R. Feit, R. Kinouchi, T.S. Kern, D.F. Chen; Using C57BL/6J as a mouse model for diabetic retinopathy . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3253.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Establish a timeline for the development of diabetic retinopathy in the C57BL/6J mouse. Methods: Diabetes was induced in mice using streptozotocin injection. Once mice had a documented elevated blood sugar (>250 mg/dl) they were maintained without insulin. Mice were sacrificed at 1, 2, 6, 12, 15, and 19 months of diabetes. Several parameters were measured to evaluate the development of diabetic retinopathy including: basement membrane thickening, acellular capillary development, TUNEL staining, and GFAP expression. Transmission electron microscopy was performed in retinal sections to measure basement membrane thickness. GFAP expression was evaluated through immunohistochemical staining and western blots. Results: Diabetic C57BL/6J mice develop hyperglycemia ranging from a glycated hemoglobin (GHb) level of 9% to 20.9%. Mice with a lower GHb had a lower level of GFAP expression compared to their littermates with more elevated GHb at 1 and 2 months on western blot. The vascular changes of diabetic retinopathy were detectable, on average, after 15–19 months of diabetes in the C57BL/6J mouse. Increased TUNEL staining and increased acellular capillaries were detected in trypsin–digested retinas of mice at 15 and 19 months of diabetes. Basement membrane thickening occured in both control and diabetic mice with aging and began to show increased thickening in the diabetic population at 15 months. Conclusions: The C57BL/6J mouse develops the changes characteristic of diabetic retinopathy after 15 to 19 months of diabetes. There is, however, significant variation in the percentage of glycated hemoglobin and it is possible that by focusing specifically on mice with more pronounced hyperglycemia the changes of diabetic retinopathy could be found at an earlier time point.
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