title: MicroRNA regulation in an animal model of acute ocular hypertension.
abstract: OBJECTIVE
  To analyse miRNA 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 miRNA 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 miRNAs microarray analysis revealed 31 differentially expressed miRNAs in the AOH versus control group, and the regulation of 12 selected microRNAs was further confirmed by qRT-PCR. Bioinformatic analysis indicates that several signalling pathways are putatively regulated by the validated miRNAs. 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 miRNAs, whose target genes were associated with the regulation of microglia-mediated neuroinflammation or neural apoptosis. Addressing miRNAs 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.
authors.affiliation: Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, China.|Eye Center of Shandong University, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, University of Murcia and Murcian Institute of Biosanitary Research-Hospital Arrixaca (IMIB-Arrixaca), Murcia, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Valiente-Soriano
authors.affiliation: Department of Ophthalmology, University of Murcia and Murcian Institute of Biosanitary Research-Hospital Arrixaca (IMIB-Arrixaca), Murcia, Spain.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Nadal-Nicolás
authors.affiliation: Department of Ophthalmology, University of Murcia and Murcian Institute of Biosanitary Research-Hospital Arrixaca (IMIB-Arrixaca), Murcia, Spain.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rovere
authors.affiliation: Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Shida
authors.initials: S
authors.lastname: Chen
authors.affiliation: Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, University of Murcia and Murcian Institute of Biosanitary Research-Hospital Arrixaca (IMIB-Arrixaca), Murcia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Agudo-Barriuso
authors.affiliation: Department of Ophthalmology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
authors.forename: Jost B
authors.identifier: http://orcid.org/0000-0003-2972-5227
authors.initials: JB
authors.lastname: Jonas
authors.affiliation: Department of Ophthalmology, University of Murcia and Murcian Institute of Biosanitary Research-Hospital Arrixaca (IMIB-Arrixaca), Murcia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vidal-Sanz
authors.affiliation: Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D004195:Disease Models, Animal; D005260:Female; D007429:Intraocular Pressure; D035683:MicroRNAs / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009693:Nucleic Acid Hybridization; D009798:Ocular Hypertension / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs
keywords: acute glaucoma model; acute ocular hypertension; microRNA; optic nerve damage; retinal ganglion cells; retinal ischaemia; retinal microglia