The role of deregulated micrornas in age-related macular degeneration pathology

Elshelmani, Hanan and Wride, Michael A. and Saad, Tahira and Rani, Sweta and Kelly, David J. and Keegan, David (2021) The role of deregulated micrornas in age-related macular degeneration pathology. Translational Vision Science and Technology, 10 (2). pp. 1-19. ISSN 2164-2591

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Abstract

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 signal-ing, apoptosis, and neurodegenerative pathways. The study also provides supporting evidence for the involvement of serum-isolated AMD-derived exosomes in the pathol-ogy 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.

Item Type:	Article
Additional Information:	Funding Information: The authors are grateful to the Irish Research Council for Science, Engineering and Technol-ogy/EMBARK Initiative, the Mater Vision Institute, the Libyan Ministry of Higher Education and Scientific Research (The Arab Medical University) for their support, Fighting Blindness Ireland (FB14 SAA), and funders of the CARMA trial (Waterford Institute of Technology). Financial support was provided by the Irish Research Council for Science, Engineering and Technology/EMBARKS Initiative, the Mater Vision Institute, the Libyan Ministry of Higher Education and Scientific Research, Fighting Blindness Ireland (FB14 SAA), and funders of CARMA trial (Waterford Institute of Technology). Funding Information: Financial support was provided by the Irish Research Council for Science, Engineering and Technology/EMBARKS Initiative, the Mater Vision Institute, the Libyan Ministry of Higher Education and Scientific Research, Fighting Blindness Ireland (FB14 SAA), and funders of CARMA trial (Waterford Institute of Technology). Funding Information: The authors are grateful to the Irish Research Council for Science, Engineering and Technology/EMBARK Initiative, the Mater Vision Institute, the Libyan Ministry of Higher Education and Scientific Research (The Arab Medical University) for their support, Fighting Blindness Ireland (FB14 SAA), and funders of the CARMA trial (Waterford Institute of Technology). Publisher Copyright: © 2021 The Authors.
Uncontrolled Keywords:	/dk/atira/pure/subjectarea/asjc/2200/2204
Departments or Groups:
Depositing User:	Admin SSL
Date Deposited:	19 Oct 2022 23:08
Last Modified:	10 Aug 2023 16:05
URI:	http://repository-testing.wit.ie/id/eprint/4237

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