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J. Oh, K. Huh, C. Oh, T. Lee; The Effects of Blood Sugar Control by Rosiglitazone Maleate on Retinal Gene Expressions of Spontaneous Diabetic Rats . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3104.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Recently, Otsuka Long–Evans Tokushima Fatty (OLETF) rat has developed for studying on type 2 diabetes. The purpose of this study is to evaluate the effect of blood sugar control by orally administered rosiglitazone maleate on the large scale change of retinal gene expression, especially diabetic retinopathy related gene profile. Methods: After the extraction of retina from Long–Evans Tokushima Otsuka (LETO) rats, non–treated , rosiglitazone–treated and fenofibrate–treated OLETF rats at 26 and 40 weeks after birth, the author studied the difference of retinal gene expression pattern between groups with microarrays. Western blot for several genes was done to verify the microarray results. The rat GeneFilter contains a total of 1152 genes, of which 1111 genes are known genes and the remaining 41 genes are expressed sequence tags (ESTs). Results: At 26 weeks after birth, 58 of retinal genes in non–treated OLETF rats were identified with expression levels that differed by more than twofold, compared with that in LETO rats. Thirteen of these were normalized by rosiglitazone. By 40 weeks after birth, the number of genes displaying more than twofold difference in expression pattern was increased to 62 genes. Only 6 genes were normalized by rosiglitazone at that time. These effects of resiglitazone were more than that of fenofibrate. The expressions of 66 genes in rosiglitazone–treated OLETF rats were increased or decreased by more than twofold than non–treated OLETF rats in 26 weeks. In 40 weeks, corresponding gene numbers were 50. Among the known genes related to diabetic retinopathy, integrin alpha V and nitric oxide synthase 3 were down–regulated. In contrast, ADAM9, laminin gamma 2 and basic FGF were up–regulated. Selectin L, superoxide dismutase 1 and caspase 9 were up or down–regulated at different time. But angiogenic growth factors except bFGF were not influenced by rosiglitazone. Conclusions: Rosiglitazone altered the expression of several genes in OLETF rats. And gene expression profiling after rosiglitazone treatment in diabetic rat retina may help in development of potential drug targets and markers for monitoring the course of disease.
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