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Anne R. Murray, Yusuke Takahashi, Jian-xing Ma; Micro-RNA (miR)-200b, a Regulator of Oxidation Resistance 1 (Oxr1), and miR-1224, a Regulator of Blue Cone Opsin (Opn1sw), are Differentially Expressed in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5941.
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MicroRNAs (miRNAs) are non-protein-coding RNAs that are involved in post-transcriptional gene regulation. Our objective was to determine whether miR-200b, a miRNA that is up-regulated in the retina of the Type 1 diabetic Akita mouse model, regulates oxidation resistance 1 (Oxr1), vascular endothelial growth factor (Vegfa and Vegfc) and hypoxia up-regulated protein 1 (Hyou1). In addition, we wanted to determine if miR-1224, a miRNA that is down-regulated in the Akita retina, regulates blue cone opsin (Opn1sw) and vascular endothelial growth factor (Vegfa).
Microarray analysis was used to examine the miRNA expression profile of the 9-month Akita mouse retina. Quantitative RT-PCR was used to confirm the microarray results of selected miRNAs. Bioinformatic analysis determined possible downstream gene targets of miR-200b and miR-1224. Target gene sequences were cloned into a dual luciferase reporter vector and a luciferase assay was used to determine whether miR-200b regulates Oxr1, Vegfa, Vegfc and Hyou1 as well if miR-1224 regulates Opn1sw and Vegfa.
miR-200b is significantly up-regulated in the Akita retina by 2.5 fold compared to the age-matched non-diabetic retina; miR-1224 is significantly down-regulated by 2.7 fold. Bioinformatics identified Oxr1, Vegfa, Vegfc and Hyou1 as possible target genes of miR-200b; Opn1sw and Vegfa were identified as possible target genes of miR-1224. A luciferase activity assay showed that of the genes analyzed, Oxr1 is regulated by miR-200b and that Opn1sw is regulated by miR-1224.
miR-200b is a regulator of Oxr1, suggesting that negative regulation of Oxr1 may be involved in regulating oxidative stress in the diabetic retina. In addition, miR-1224 regulates Opn1sw, suggesting that there may be a mechanism by which the diabetic retina attempts to compensate for visual function loss through increased cone opsin production.
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