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MicroRNA profile of the developing mouse retina.

ABSTRACT: Purpose. MicroRNAs (miRNAs) are short, noncoding transcripts that negatively regulate gene expression. They are implicated in diverse cellular processes. The purpose of this study was to obtain a global expression profile of miRNAs in the developing retina and identify differences in miRNA expression between adult rod and cone photoreceptors. Methods. Locked nucleic acid (LNA) microarrays were used to investigate the miRNA transcriptome of the developing mouse retina and brain. Real-time PCR was used to validate the array findings. Laser capture microdissection was used to determine the miRNA spatial pattern of expression. Results. One hundred thirty-eight miRNAs were expressed at at least one of the investigated time points. Several miRNAs showed significant changes in expression between embryonic day 15 and adult age in both retina and brain. Cluster analysis identified subgroups of miRNAs showing defined expression profiles. Globally, correlation of expression was higher, with increasing sequence similarity of the mature miRNAs. The miRNAs with identical seed sequences exhibited highly correlated expression profiles. The co-expression of selected host gene and intronic miRNA pairs was confirmed in adult retina. In some cases, expression profiles of miRNAs showed weak correlation with those of their host transcripts, suggesting posttranscriptional regulation of miRNAs during development. In addition, the miRNA transcriptome of rod- and cone-dominant retinas showed only minor differences, and no miRNAs specific for either cell-type were identified. Conclusions. Global expression profiling revealed dozens of miRNAs with significant expression changes in the developing retina. Precise patterns of expression of miRNAs suggest their specific roles in development.

SUBMITTER: Hackler L

PROVIDER: S-EPMC2868396 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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MicroRNA profile of the developing mouse retina.

Hackler Laszlo L Wan Jun J Swaroop Anand A Qian Jiang J Zack Donald J DJ

Investigative ophthalmology & visual science 20091120 4

Purpose. MicroRNAs (miRNAs) are short, noncoding transcripts that negatively regulate gene expression. They are implicated in diverse cellular processes. The purpose of this study was to obtain a global expression profile of miRNAs in the developing retina and identify differences in miRNA expression between adult rod and cone photoreceptors. Methods. Locked nucleic acid (LNA) microarrays were used to investigate the miRNA transcriptome of the developing mouse retina and brain. Real-time PCR was ...[more]

PMID: 19933188

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Project description:BackgroundIschemic 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 & methodsUsing Next Generation Sequencing (NGS) we profiled miRNA expression in the retina and choroid during vasodegenerative and NV phases of oxygen-induced retinopathy (OIR).ResultsApproximately 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.ConclusionThe 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.

Dataset Information

MicroRNA profile of the developing mouse retina.

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MicroRNA profile of the developing mouse retina.

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