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K. E. Guziewicz, M. Thiersch, C. Grimm; Identification of Hypoxia Regulated MicroRNAs in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2057.
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MicroRNAs, the newly recognized regulators of translation and stability of mRNA, affect and control a diverse range of normal and pathological cellular processes.Retinal cells exposed to hypoxia respond by increasing the stability of HIF-1, a major hypoxic signaling protein that activates transcription of numerous genes mediating i. a. cell survival. This study focuses on the identification of miRNAs linked to the HIF1-inducible genes as potential modifiers of photoreceptor cell survival in mouse retina.
Adult wild-type mice were exposed to 6% O2 for 6h. Total RNA from retinas pooled as triplicates was purified using TRIzol reagent (Invitrogen) immediately after preconditioning or after 2 or 4h of reoxygenation. MiRNA expression profile of hypoxic and normoxic samples were analyzed on miRCURYTM LNA microRNAs Arrays (Exiqon) containing 488 miRNA probes. MiRNA targets were detected in silico (http://microrna.sanger.ac.uk/).
Global miRNAs expression pattern in hypoxic and normoxic retinas have been profiled using microarray-based screening. Significant differences in the expression pattern of miRNAs have been identified. Comparative analysis between specific time points of hypoxic preconditioning revealed an altered miRNA profiles, particularly among samples analyzed immediately after hypoxic exposure. Potential target genes for most differentially expressed miRNAs, including transcripts linked to HIF1-inducible genes have been assigned.
The preliminary results indicate that miRNAs might be involved in the regulation of the retinal response to hypoxia. The suggested modulatory role of specific miRNAs for the expression of HIF-1 target genes may connect microRNAs with the cell survival and neuroprotection.
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