Dataset Information

Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development.

ABSTRACT: Tyrosine phosphatase STEP (striatal-enriched tyrosine protein phosphatase) is a brain-specific protein phosphatase and is involved in the pathogenesis of many neurodegenerative diseases. Here, we examined the impact of STEP on the development of age-related macular degeneration (AMD)-like pathology in senescence-accelerated OXYS rats. Using OXYS and Wistar rats (control), we for the first time demonstrated age-dependent changes in Ptpn5 mRNA expression, STEP46 and STEP61 protein levels, and their phosphatase activity in the retina. The increases in STEP protein levels and the decrease of total and STEP phosphatase activities in the retina (as compared with Wistar rats) preceded the manifestation of clinical signs of AMD in OXYS rats (age 20 days). There were no differences in these retinal parameters between 13-month-old Wistar rats and OXYS rats with pronounced signs of AMD. Inhibition of STEP with TC-2153 during progressive AMD-like retinopathy (from 9 to 13 months of age) reduced the thickness of the retinal inner nuclear layer, as evidenced by a decreased amount of parvalbumin-positive amacrine neurons. Prolonged treatment with TC-2153 had no effect on Ptpn5 mRNA expression, STEP46 and STEP61 protein levels, and their phosphatase activity in the OXYS retina. Thus, TC-2153 may negatively affect the retina through mechanisms unrelated to STEP.

SUBMITTER: Telegina DV

PROVIDER: S-EPMC7432912 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development.

Telegina Darya V DV Kulikova Elizabeth A EA Kozhevnikova Oyuna S OS Kulikov Alexander V AV Khomenko Tatyana M TM Volcho Konstantin P KP Salakhutdinov Nariman F NF Kolosova Nataliya G NG

International journal of molecular sciences 20200722 15

Tyrosine phosphatase STEP (striatal-enriched tyrosine protein phosphatase) is a brain-specific protein phosphatase and is involved in the pathogenesis of many neurodegenerative diseases. Here, we examined the impact of STEP on the development of age-related macular degeneration (AMD)-like pathology in senescence-accelerated OXYS rats. Using OXYS and Wistar rats (control), we for the first time demonstrated age-dependent changes in <i>Ptpn5</i> mRNA expression, STEP46 and STEP61 protein levels, a ...[more]

PMID: 32707818

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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

Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development.

Publications

Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development.

Similar Datasets

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