MicroRNA regulation in an animal model of acute ocular hypertension.

Purpose To analyse mi RNA regulation in a rat model of acute ocular hypertension ( AOH). Methods Acute ocular hypertension (AOH) was induced in the left eye of adult albino rats by inserting a cannula connected with a saline container into the anterior chamber. The contralateral eye served as a control. Seven days later, animals were killed. Retinas were used either for quantitative analysis of retinal ganglion cells ( RGCs) and microglial cells or for mi RNA array hybridization, qRT- PCR and Western blotting. Results Anatomically, AOH caused axonal degeneration, a significant loss of RGCs and a significant increase in microglial cells in the ganglion cell layer. The mi RNAs microarray analysis revealed 31 differentially expressed mi RNAs in the AOH versus control group, and the regulation of 12 selected micro RNAs was further confirmed by qRT- PCR. Bioinformatic analysis indicates that several signalling pathways are putatively regulated by the validated mi RNAs. Of particular interest was the inflammatory pathway signalled by mitogen-activated protein kinases ( MAPKs). In agreement with the in silico analysis, p38 MAP kinase, tumour necrosis factor-alpha ( TNF-α) and iNOS proteins were significantly upregulated in the AOH retinas. Conclusions Acute IOP elevation led to changes in the expression of mi RNAs, whose target genes were associated with the regulation of microglia-mediated neuroinflammation or neural apoptosis. Addressing mi RNAs in the process of retinal ischaemia and optic nerve damage in association with high IOP elevation may open new avenues in preventing retinal ganglion cell apoptosis and may serve as target for future therapeutic regimen in acute ocular hypertension and retinal ischaemic conditions. [ABSTRACT FROM AUTHOR]

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