MicroRNA expression profile in retina and choroid in oxygen-induced retinopathy model

• Published in: PloS one Vol. 14; no. 6; p. e0218282
• Main Authors: Desjarlais, Michel, Rivera, Jose Carlos, Lahaie, Isabelle, Cagnone, Gaël, Wirt, Maëlle, Omri, Samy, Chemtob, Sylvain
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.06.2019; Public Library of Science (PLoS)
• Subjects: Algorithms; Angiogenesis; Animals; Animals, Newborn; Apoptosis; Biochemistry; Biology and life sciences; Blood vessels; Cell adhesion & migration; Choroid - drug effects; Choroid - metabolism; Choroid - pathology; Criminal investigation; Degeneration; Departments; Diabetes; Diabetic retinopathy; Diagnosis; Disease Models, Animal; Eye Abnormalities - chemically induced; Eye Abnormalities - genetics; Eye Abnormalities - metabolism; Eye Abnormalities - pathology; Eye Proteins - genetics; Eye Proteins - metabolism; Gene expression; Gene Expression Regulation; Genes; High-Throughput Nucleotide Sequencing; Humans; Hyperoxia; Inflammation; Ischemia; Ischemia - genetics; Ischemia - metabolism; Ischemia - pathology; Medicine and Health Sciences; MicroRNA; MicroRNAs; MicroRNAs - classification; MicroRNAs - genetics; MicroRNAs - metabolism; Microvasculature; miRNA; Neovascularization; Next-generation sequencing; Oxidative stress; Oxygen; Oxygen - toxicity; Pathology; Pediatrics; People with disabilities; Pharmacology; Physiology; Post-transcription; Rats; Rats, Sprague-Dawley; Research and analysis methods; Retina; Retina - drug effects; Retina - metabolism; Retina - pathology; Retinal diseases; Retinal Neovascularization - chemically induced; Retinal Neovascularization - genetics; Retinal Neovascularization - metabolism; Retinal Neovascularization - pathology; Retinal Vessels - abnormalities; Retinal Vessels - metabolism; Retinal Vessels - pathology; Retinitis - chemically induced; Retinitis - genetics; Retinitis - metabolism; Retinitis - pathology; Retinopathy; Ribonucleic acid; Risk factors; RNA; Rodents; Signal Transduction; Target recognition; Technology; Vascular Malformations - chemically induced; Vascular Malformations - genetics; Vascular Malformations - metabolism; Vascular Malformations - pathology; Vascularization; Canada; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0218282

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