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Ricky Zhenghao Cui, Chi-Hsiu Liu, Aimee Marie Juan, Lucy Evans, Katherine Tian, Jing Chen; MicroRNA expression array analysis in a mouse model of oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):47.
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© ARVO (1962-2015); The Authors (2016-present)
Retinopathy of prematurity (ROP) is a leading cause of blindness in children. To improve upon current invasive surgical treatments, a better understanding of the molecular control systems in the pathogenesis of ROP is needed to identify preventative and less-invasive therapies. MicroRNAs (miRNAs), a group of small non-coding regulatory RNAs, have been shown to play critical roles in both vascular and neuronal development of retina, as well as in pathologic angiogenesis. Here we assess the expression profile of retinal microRNAs in a mouse model of oxygen-induced retinopathy (OIR) modeling ROP in humans, in an effort to identify the function and therapeutic potential of specific microRNAs in retinopathy.
Neonatal C57BL/6J mice were exposed to 75% oxygen from postnatal (P) 7 to P 12 to induce retinopathy. MicroRNA expression array analysis (Affymetrix GeneChip miRNA array) was used to assess miRNA expression profile in P17 OIR retinas compared to age-matched room air control retinas (n=3 per group). Selected miRNAs were validated with RT-qPCR. Putative target genes of significantly altered miRNAs were analyzed with softwares Targetscan and miRbase.
We identified more than 20 microRNAs that are significantly upregulated in OIR retinas and more than 20 miRNAs that are downregulated. Upregulated miRNAs include miR-351, miR-762, miR-210, miR-145 and miR-214. Downregulated miRNAs include miR-129-5p, miR-129-3p, miR-150, miR-203, and miR-375. In particular, the expression of miR-150 is significantly suppressed up to 5 fold in OIR retinas compared to age matched room air controls as confirmed by qRT-PCR (n = 6 per group, p ≤ 0.05). Bioinformatics analysis showed that multiple regulated miRNAs have predicted target genes in angiogenic and/or inflammatory pathways.
Our findings indicate that multiple miRNAs are significantly altered in OIR retinas, which may exert critical post-transcriptional regulatory roles in pathological retinal neovascularization through potentially influencing angiogenesis and inflammation processes important for retinopathy. Further analysis of these miRNAs will help determine their function and therapeutic potential in ROP.
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