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The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology.
Transl Vis Sci Technol. 2021 02 05; 10(2):12.TV

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 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.

Links

PMC Free PDF

Authors+Show Affiliations

ElShelmani H
Ocular Development and Neurobiology Research Group, Zoology Department, School of Natural Sciences, University of Dublin, Trinity College Dublin, Dublin 2, Ireland. Mater Retina Research Group, Mater Misericordiae University Hospital, Eccles St., Dublin 7, Ireland.
Wride MA
Ocular Development and Neurobiology Research Group, Zoology Department, School of Natural Sciences, University of Dublin, Trinity College Dublin, Dublin 2, Ireland.
Saad T
Mater Retina Research Group, Mater Misericordiae University Hospital, Eccles St., Dublin 7, Ireland.
Rani S
Department of Science, Waterford Institute of Technology, Waterford, Ireland.
Kelly DJ
Zoology Department, School of Natural Sciences, University of Dublin, Trinity College Dublin, Ireland.
Keegan D
Mater Retina Research Group, Mater Misericordiae University Hospital, Eccles St., Dublin 7, Ireland.

MeSH

Computational BiologyExosomesHumansMacular DegenerationMicroRNAsVascular Endothelial Growth Factor A

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34003896

Citation

ElShelmani, Hanan, et al. "The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology." Translational Vision Science & Technology, vol. 10, no. 2, 2021, p. 12.
ElShelmani H, Wride MA, Saad T, et al. The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology. Transl Vis Sci Technol. 2021;10(2):12.
ElShelmani, H., Wride, M. A., Saad, T., Rani, S., Kelly, D. J., & Keegan, D. (2021). The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology. Translational Vision Science & Technology, 10(2), 12. https://doi.org/10.1167/tvst.10.2.12
ElShelmani H, et al. The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology. Transl Vis Sci Technol. 2021 02 5;10(2):12. PubMed PMID: 34003896.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Role of Deregulated MicroRNAs in Age-Related Macular Degeneration Pathology. AU - ElShelmani,Hanan, AU - Wride,Michael A, AU - Saad,Tahira, AU - Rani,Sweta, AU - Kelly,David J, AU - Keegan,David, PY - 2021/5/18/entrez PY - 2021/5/19/pubmed PY - 2021/6/29/medline SP - 12 EP - 12 JF - Translational vision science & technology JO - Transl Vis Sci Technol VL - 10 IS - 2 N2 - 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. SN - 2164-2591 UR - https://www.unboundmedicine.com/medline/citation/34003896/The_Role_of_Deregulated_MicroRNAs_in_Age_Related_Macular_Degeneration_Pathology_ DB - PRIME DP - Unbound Medicine ER -