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The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology
PURPOSE: We previously identified three microRNAs (miRNAs) with significantly increased expression in the serum of patients with age-related macular degeneration (AMD) compared with healthy controls. Our objective was to identify potential functional roles of these upregulated miRNAs (miR-19a, miR-1...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881277/ https://www.ncbi.nlm.nih.gov/pubmed/34003896 http://dx.doi.org/10.1167/tvst.10.2.12 |
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author | ElShelmani, Hanan Wride, Michael A. Saad, Tahira Rani, Sweta Kelly, David J. Keegan, David |
author_facet | ElShelmani, Hanan Wride, Michael A. Saad, Tahira Rani, Sweta Kelly, David J. Keegan, David |
author_sort | ElShelmani, Hanan |
collection | PubMed |
description | PURPOSE: We previously identified three microRNAs (miRNAs) with significantly increased expression in the serum of patients with age-related macular degeneration (AMD) compared with healthy controls. Our objective was to identify potential functional roles of these upregulated miRNAs (miR-19a, miR-126, and miR-410) in AMD, using computational tools for miRNAs prediction and identification, and to demonstrate the miRNAs target genes and signaling pathways. We also aim to demonstrate the pathologic role of isolated sera-derived exosomes from patients with AMD and controls using in vitro models. METHODS: miR-19a, miR-126, and miR-410 were investigated using bioinformatic approaches, including DIANA-mirPath and miR TarBase. Data on the resulting target genes and signaling pathways were incorporated with the differentially expressed miRNAs in AMD. Apoptosis markers, human apoptosis miRNAs polymerase chain reaction arrays and angiogenesis/vasculogenesis assays were performed by adding serum-isolated AMD patient or control patient derived exosomes into an in vitro human angiogenesis model and ARPE-19 cell lines. RESULTS: A number of pathways known to be involved in AMD development and progression were predicted, including the vascular endothelial growth factor signaling, apoptosis, and neurodegenerative pathways. The study also provides supporting evidence for the involvement of serum-isolated AMD-derived exosomes in the pathology of AMD, via apoptosis and/or angiogenesis. CONCLUSIONS: miR-19a, miR-126, miR-410 and their target genes had a significant correlation with AMD pathogenesis. As such, they could be potential new targets as predictive biomarkers or therapies for patients with AMD. TRANSLATIONAL RELEVANCE: The functional analysis and the pathologic role of altered miRNA expression in AMD may be applicable in developing new therapies for AMD through the disruption of individual or multiple pathophysiologic pathways. |
format | Online Article Text |
id | pubmed-7881277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-78812772021-02-18 The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology ElShelmani, Hanan Wride, Michael A. Saad, Tahira Rani, Sweta Kelly, David J. Keegan, David Transl Vis Sci Technol Article PURPOSE: We previously identified three microRNAs (miRNAs) with significantly increased expression in the serum of patients with age-related macular degeneration (AMD) compared with healthy controls. Our objective was to identify potential functional roles of these upregulated miRNAs (miR-19a, miR-126, and miR-410) in AMD, using computational tools for miRNAs prediction and identification, and to demonstrate the miRNAs target genes and signaling pathways. We also aim to demonstrate the pathologic role of isolated sera-derived exosomes from patients with AMD and controls using in vitro models. METHODS: miR-19a, miR-126, and miR-410 were investigated using bioinformatic approaches, including DIANA-mirPath and miR TarBase. Data on the resulting target genes and signaling pathways were incorporated with the differentially expressed miRNAs in AMD. Apoptosis markers, human apoptosis miRNAs polymerase chain reaction arrays and angiogenesis/vasculogenesis assays were performed by adding serum-isolated AMD patient or control patient derived exosomes into an in vitro human angiogenesis model and ARPE-19 cell lines. RESULTS: A number of pathways known to be involved in AMD development and progression were predicted, including the vascular endothelial growth factor signaling, apoptosis, and neurodegenerative pathways. The study also provides supporting evidence for the involvement of serum-isolated AMD-derived exosomes in the pathology of AMD, via apoptosis and/or angiogenesis. CONCLUSIONS: miR-19a, miR-126, miR-410 and their target genes had a significant correlation with AMD pathogenesis. As such, they could be potential new targets as predictive biomarkers or therapies for patients with AMD. TRANSLATIONAL RELEVANCE: The functional analysis and the pathologic role of altered miRNA expression in AMD may be applicable in developing new therapies for AMD through the disruption of individual or multiple pathophysiologic pathways. The Association for Research in Vision and Ophthalmology 2021-02-10 /pmc/articles/PMC7881277/ /pubmed/34003896 http://dx.doi.org/10.1167/tvst.10.2.12 Text en Copyright 2021 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. |
spellingShingle | Article ElShelmani, Hanan Wride, Michael A. Saad, Tahira Rani, Sweta Kelly, David J. Keegan, David The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology |
title | The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology |
title_full | The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology |
title_fullStr | The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology |
title_full_unstemmed | The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology |
title_short | The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology |
title_sort | role of deregulated micrornas in age-related macular degeneration pathology |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881277/ https://www.ncbi.nlm.nih.gov/pubmed/34003896 http://dx.doi.org/10.1167/tvst.10.2.12 |
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