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J. Oh, K. Huh, S. Kim, T. Lee; Retinal gene expression in spontaneous diabetic rats(Otsuka Long–Evans Tokushima Fatty rats) . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2475.
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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. This study is to investigate the difference of retinal gene expression pattern between Otsuka Long–Evans Tokushima Fatty rats for type 2 diabetes and Long–Evans Tokushima Otsuka(LETO) rats as normal control using microarray. Methods: The author studied on the retinal gene expression profile of OLETF rats at 18 months and 40 months with microarrays after the extraction of retina from OLETF rats and LETO rats. Genes were sorted into clusters according to their temporal expression profiles. They were also grouped according to their potential pathophysiological significance. 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 18 weeks after birth, 53 genes were identified with expression levels that differed by more than twofold, compared with that in control group. The expression of 32 genes were increased by twofold or more, whereas expression of 21 genes were decreased by twofold or more. By 40 week after birth, the number of genes displaying more than twofold difference in expression pattern was increased to 62 genes; 44 genes, elevated levels, 18 genes, decreased levels. Genes related to leukocyte adhesion (ICAM–1, endothelial selectin, integrin alpha V), protein kinase C eta, iota, heat shock protein and nitric oxide synthase 3(endothelial cell) were upregulated. However upregulation of CD44 and downregulation of aquaporin 1 are different from previous reports. Especially upregulation of PDGF beta polypeptide at 18 weeks and downregulation at 40 weeks are interesting finding. It may be related to pericyte loss in the early stage of diabetic retina. Conclusions: Nine clusters of genes were identified with very similar patterns of expression. This study would suggest that a common regulatory pathway for the genes exist within a cluster, and their identification may provide potential role in new targets of regulating diabetic retinopathy.
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