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MicroRNA expression profile in retina and choroid in oxygen-induced retinopathy model.
PLoS One. 2019; 14(6):e0218282.Plos

Abstract

BACKGROUND

Ischemic retinopathies (IRs) are leading causes of visual impairment. They are characterized by an initial phase of microvascular degeneration and a second phase of aberrant pre-retinal neovascularization (NV). microRNAs (miRNAs) regulate gene expression, and a number play a role in normal and pathological NV. But, post-transcriptional modulation of miRNAs in the eye during the development of IRs has not been systematically evaluated.

AIMS & METHODS

Using Next Generation Sequencing (NGS) we profiled miRNA expression in the retina and choroid during vasodegenerative and NV phases of oxygen-induced retinopathy (OIR).

RESULTS

Approximately 20% of total miRNAs exhibited altered expression (up- or down-regulation); 6% of miRNA were found highly expressed in retina and choroid of rats subjected to OIR. During OIR-induced vessel degeneration phase, miR-199a-3p, -199a-5p, -1b, -126a-3p displayed a robust decreased expression (> 85%) in the retina. While in the choroid, miR-152-3p, -142-3p, -148a-3p, -532-3p were upregulated (>200%) and miR-96-5p, -124-3p, -9a-3p, -190b-5p, -181a-1-3p, -9a-5p, -183-5p were downregulated (>70%) compared to controls. During peak pathological NV, miR-30a-5p, -30e-5p and 190b-5p were markedly reduced (>70%), and miR-30e-3p, miR-335, -30b-5p strongly augmented (by up to 300%) in the retina. Whereas in choroid, miR-let-7f-5p, miR-126a-5p and miR-101a-3p were downregulated by (>81%), and miR-125a-5p, let-7e-5p and let-7g-5p were upregulated by (>570%) during NV. Changes in miRNA observed using NGS were validated using qRT-PCR for the 24 most modulated miRNAs. In silico approach to predict miRNA target genes (using algorithms of miRSystem database) identified potential new target genes with pro-inflammatory, apoptotic and angiogenic properties.

CONCLUSION

The present study is the first comprehensive description of retinal/choroidal miRNAs profiling in OIR (using NGS technology). Our results provide a valuable framework for the characterization and possible therapeutic potential of specific miRNAs involved in ocular IR-triggered inflammation, angiogenesis and degeneration.

Links

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Authors+Show Affiliations

Desjarlais M
Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, University of Montréal, Montréal, Québec, Canada.
Rivera JC
Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, University of Montréal, Montréal, Québec, Canada. Departments of Pediatrics, Ophthalmology and Pharmacology, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, Québec, Canada.
Lahaie I
Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, University of Montréal, Montréal, Québec, Canada.
Cagnone G
Departments of Pediatrics, Ophthalmology and Pharmacology, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, Québec, Canada.
Wirt M
Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, University of Montréal, Montréal, Québec, Canada.
Omri S
Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, University of Montréal, Montréal, Québec, Canada.
Chemtob S
Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, University of Montréal, Montréal, Québec, Canada. Departments of Pediatrics, Ophthalmology and Pharmacology, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, Québec, Canada.

MeSH

AnimalsAnimals, NewbornChoroidDisease Models, AnimalEye AbnormalitiesEye ProteinsGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansIschemiaMicroRNAsOxygenRatsRats, Sprague-DawleyRetinaRetinal NeovascularizationRetinal VesselsRetinitisSignal TransductionVascular Malformations

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31188886

Citation

Desjarlais, Michel, et al. "MicroRNA Expression Profile in Retina and Choroid in Oxygen-induced Retinopathy Model." PloS One, vol. 14, no. 6, 2019, pp. e0218282.
Desjarlais M, Rivera JC, Lahaie I, et al. MicroRNA expression profile in retina and choroid in oxygen-induced retinopathy model. PLoS One. 2019;14(6):e0218282.
Desjarlais, M., Rivera, J. C., Lahaie, I., Cagnone, G., Wirt, M., Omri, S., & Chemtob, S. (2019). MicroRNA expression profile in retina and choroid in oxygen-induced retinopathy model. PloS One, 14(6), e0218282. https://doi.org/10.1371/journal.pone.0218282
Desjarlais M, et al. MicroRNA Expression Profile in Retina and Choroid in Oxygen-induced Retinopathy Model. PLoS One. 2019;14(6):e0218282. PubMed PMID: 31188886.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA expression profile in retina and choroid in oxygen-induced retinopathy model. AU - Desjarlais,Michel, AU - Rivera,Jose Carlos, AU - Lahaie,Isabelle, AU - Cagnone,Gaël, AU - Wirt,Maëlle, AU - Omri,Samy, AU - Chemtob,Sylvain, Y1 - 2019/06/12/ PY - 2019/02/16/received PY - 2019/05/29/accepted PY - 2019/6/13/entrez PY - 2019/6/13/pubmed PY - 2020/2/15/medline SP - e0218282 EP - e0218282 JF - PloS one JO - PLoS One VL - 14 IS - 6 N2 - BACKGROUND: Ischemic retinopathies (IRs) are leading causes of visual impairment. They are characterized by an initial phase of microvascular degeneration and a second phase of aberrant pre-retinal neovascularization (NV). microRNAs (miRNAs) regulate gene expression, and a number play a role in normal and pathological NV. But, post-transcriptional modulation of miRNAs in the eye during the development of IRs has not been systematically evaluated. AIMS & METHODS: Using Next Generation Sequencing (NGS) we profiled miRNA expression in the retina and choroid during vasodegenerative and NV phases of oxygen-induced retinopathy (OIR). RESULTS: Approximately 20% of total miRNAs exhibited altered expression (up- or down-regulation); 6% of miRNA were found highly expressed in retina and choroid of rats subjected to OIR. During OIR-induced vessel degeneration phase, miR-199a-3p, -199a-5p, -1b, -126a-3p displayed a robust decreased expression (> 85%) in the retina. While in the choroid, miR-152-3p, -142-3p, -148a-3p, -532-3p were upregulated (>200%) and miR-96-5p, -124-3p, -9a-3p, -190b-5p, -181a-1-3p, -9a-5p, -183-5p were downregulated (>70%) compared to controls. During peak pathological NV, miR-30a-5p, -30e-5p and 190b-5p were markedly reduced (>70%), and miR-30e-3p, miR-335, -30b-5p strongly augmented (by up to 300%) in the retina. Whereas in choroid, miR-let-7f-5p, miR-126a-5p and miR-101a-3p were downregulated by (>81%), and miR-125a-5p, let-7e-5p and let-7g-5p were upregulated by (>570%) during NV. Changes in miRNA observed using NGS were validated using qRT-PCR for the 24 most modulated miRNAs. In silico approach to predict miRNA target genes (using algorithms of miRSystem database) identified potential new target genes with pro-inflammatory, apoptotic and angiogenic properties. CONCLUSION: The present study is the first comprehensive description of retinal/choroidal miRNAs profiling in OIR (using NGS technology). Our results provide a valuable framework for the characterization and possible therapeutic potential of specific miRNAs involved in ocular IR-triggered inflammation, angiogenesis and degeneration. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/31188886/MicroRNA_expression_profile_in_retina_and_choroid_in_oxygen_induced_retinopathy_model_ DB - PRIME DP - Unbound Medicine ER -