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MicroRNA regulation in an animal model of acute ocular hypertension
Author(s) -
Wang Jiawei,
ValienteSoriano Francisco J.,
NadalNicolás Francisco M.,
Rovere Giuseppe,
Chen Shida,
Huang Wenbin,
AgudoBarriuso Marta,
Jonas Jost B.,
VidalSanz Manuel,
Zhang Xiulan
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.13227
Subject(s) - ganglion cell layer , retina , ocular hypertension , microrna , biology , retinal ganglion cell , medicine , microglia , optic nerve , pathology , microbiology and biotechnology , neuroscience , immunology , glaucoma , inflammation , genetics , gene
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 ( RGC s) and microglial cells or for mi RNA array hybridization, qRT ‐ PCR and Western blotting. Results Anatomically, AOH caused axonal degeneration, a significant loss of RGC s and a significant increase in microglial cells in the ganglion cell layer. The mi RNA s microarray analysis revealed 31 differentially expressed mi RNA s in the AOH versus control group, and the regulation of 12 selected micro RNA s was further confirmed by qRT ‐ PCR . Bioinformatic analysis indicates that several signalling pathways are putatively regulated by the validated mi RNA s. Of particular interest was the inflammatory pathway signalled by mitogen‐activated protein kinases ( MAPK s). 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 RNA s, whose target genes were associated with the regulation of microglia‐mediated neuroinflammation or neural apoptosis. Addressing mi RNA s 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.