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S. J. Kirwin, S. T. Kanaly, B. J. Cairns, M. Ren, J. L. Edelman; Gene Expression Changes and Simultaneous Reduction in Visual Function in the Retina of Diabetic Long Evans Rats. Invest. Ophthalmol. Vis. Sci. 2010;51(13):113.
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© ARVO (1962-2015); The Authors (2016-present)
Patients with diabetic retinopathy may experience severe vision loss due to macular edema or neovascularization secondary to vascular abnormalities. However, prior to clinically-significant vascular abnormalities, patients may also have functional deficits in contrast sensitivity, color perception, and dark adaptation. The goals of the current study are to evaluate early changes (< 3 months) in retinal gene expression, selected visual cycle proteins, and visual acuity in Streptozotocin-induced diabetic rats.
Gene changes in the retina of diabetic Long Evans rats were measured by whole genome microarray 7 days, 4 weeks, and 3 months after onset of diabetes. Select gene and protein changes were probed by PCR and immunohistochemistry respectively, and visual acuity was measured using a virtual optokinetics system.
Microarray analysis showed that the most consistently affected molecular and cellular functions were cell-to-cell signaling and interaction, cell death, cellular growth and proliferation, molecular transport, and cellular movement. Further analysis revealed reduced expression of several genes encoding proteins associated with the visual cycle including lecithin:retinol acyltransferase (LRAT), retinal pigment epithelium-specific protein 65kDa (RPE65) and RPE retinal G protein coupled receptor (RGR). Immunohistochemistry revealed a decrease in RPE65 in the RPE layer of diabetic rats. These molecular changes occurred simultaneously with a decrease in visual acuity by 4 weeks of diabetes.
These data are further evidence that inner retinal cells are altered by hyperglycemia prior to significant vascular damage in a rat model of diabetic retinopathy. These early functional changes are correlated with novel biomarkers and a visual function deficit that may be useful to evaluate pharmacologic interventions in the future.
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