miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks
Glaucoma has no cure and is a sight-threatening neurodegenerative disease affecting more than 100 million people worldwide, with primary open angle glaucoma (POAG) being the most globally prevalent glaucoma clinical type. Regulation of gene expression and gene networks, and its multifactorial pathwa...
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2021-05-01
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author | Jorge Raga-Cervera Jose M. Bolarin Jose M. Millan Jose J. Garcia-Medina Laia Pedrola Javier Abellán-Abenza Mar Valero-Vello Silvia M. Sanz-González José E. O’Connor David Galarreta-Mira Elena Bendala-Tufanisco Aloma Mayordomo-Febrer Maria D. Pinazo-Durán Vicente Zanón-Moreno |
author_facet | Jorge Raga-Cervera Jose M. Bolarin Jose M. Millan Jose J. Garcia-Medina Laia Pedrola Javier Abellán-Abenza Mar Valero-Vello Silvia M. Sanz-González José E. O’Connor David Galarreta-Mira Elena Bendala-Tufanisco Aloma Mayordomo-Febrer Maria D. Pinazo-Durán Vicente Zanón-Moreno |
author_sort | Jorge Raga-Cervera |
collection | DOAJ |
description | Glaucoma has no cure and is a sight-threatening neurodegenerative disease affecting more than 100 million people worldwide, with primary open angle glaucoma (POAG) being the most globally prevalent glaucoma clinical type. Regulation of gene expression and gene networks, and its multifactorial pathways involved in glaucoma disease are landmarks for ophthalmic research. MicroRNAs (miRNAs/miRs) are small endogenous non-coding, single-stranded RNA molecules (18–22 nucleotides) that regulate gene expression. An analytical, observational, case-control study was performed in 42 patients of both sexes, aged 50 to 80 years, which were classified according to: (1) suffering from ocular hypertension (OHT) but no glaucomatous neurodegeneration (ND) such as the OHT group, or (2) have been diagnosed of POAG such as the POAG group. Participants were interviewed for obtaining sociodemographic and personal/familial records, clinically examined, and their tear samples were collected and frozen at 80 °C until processing for molecular-genetic assays. Tear RNA extraction, libraries construction, and next generation sequencing were performed. Here, we demonstrated, for the first time, the differential expression profiling of eight miRNAs when comparing tears from the OHT versus the POAG groups: the miR-26b-5p, miR-152-3p, miR-30e-5p, miR-125b-2-5p, miR-224-5p, miR-151a-3p, miR-1307-3p, and the miR-27a-3p. Gene information was set up from the DIANA-TarBase v7, DIANA-microT-CDS, and TargetScan v7.1 databases. To build a network of metabolic pathways, only genes appearing in at least four of the following databases: DisGeNet, GeneDistiller, MalaCards, OMIM PCAN, UniProt, and GO were considered. We propose miRNAs and their target genes/signaling pathways as candidates for a better understanding of the molecular-genetic bases of glaucoma and, in this way, to gain knowledge to achieve optimal diagnosis strategies for properly identifying HTO at higher risk of glaucoma ND. Further research is needed to validate these miRNAs to discern the potential role as biomarkers involved in oxidative stress, immune response, and apoptosis for the diagnosis and/or prognosis of OHT and the prevention of glaucoma ND. |
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issn | 2077-0383 |
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spelling | doaj.art-bc340ee2755e492b9775953182bd19472023-11-21T20:43:35ZengMDPI AGJournal of Clinical Medicine2077-03832021-05-011011222710.3390/jcm10112227miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis NetworksJorge Raga-Cervera0Jose M. Bolarin1Jose M. Millan2Jose J. Garcia-Medina3Laia Pedrola4Javier Abellán-Abenza5Mar Valero-Vello6Silvia M. Sanz-González7José E. O’Connor8David Galarreta-Mira9Elena Bendala-Tufanisco10Aloma Mayordomo-Febrer11Maria D. Pinazo-Durán12Vicente Zanón-Moreno13Hospital of Manises, 46940 Valencia, SpainTechnological Centre of Information and Communication Technologies (CENTIC), 30100 Murcia, SpainSequencing Service at the University and Polytechnic Hospital La Fe, 46026 Valencia, SpainOphthalmic Research Unit “Santiago Grisolía”/FISABIO, 46017 Valencia, SpainSequencing Service at the University and Polytechnic Hospital La Fe, 46026 Valencia, SpainTechnological Centre of Information and Communication Technologies (CENTIC), 30100 Murcia, SpainOphthalmic Research Unit “Santiago Grisolía”/FISABIO, 46017 Valencia, SpainOphthalmic Research Unit “Santiago Grisolía”/FISABIO, 46017 Valencia, SpainLaboratory of Cytomics, Joint Research Unit Principe Felipe Research Center and University of Valencia, 46010 Valencia, SpainUniversity Clinic Hospital of Valladolid, 47003 Valladolid, SpainSpanish Net of Ophthalmic Research OFTARED RD16/0008/0022, Institute of Health Carlos III., 28029 Madrid, SpainSpanish Net of Ophthalmic Research OFTARED RD16/0008/0022, Institute of Health Carlos III., 28029 Madrid, SpainOphthalmic Research Unit “Santiago Grisolía”/FISABIO, 46017 Valencia, SpainOphthalmic Research Unit “Santiago Grisolía”/FISABIO, 46017 Valencia, SpainGlaucoma has no cure and is a sight-threatening neurodegenerative disease affecting more than 100 million people worldwide, with primary open angle glaucoma (POAG) being the most globally prevalent glaucoma clinical type. Regulation of gene expression and gene networks, and its multifactorial pathways involved in glaucoma disease are landmarks for ophthalmic research. MicroRNAs (miRNAs/miRs) are small endogenous non-coding, single-stranded RNA molecules (18–22 nucleotides) that regulate gene expression. An analytical, observational, case-control study was performed in 42 patients of both sexes, aged 50 to 80 years, which were classified according to: (1) suffering from ocular hypertension (OHT) but no glaucomatous neurodegeneration (ND) such as the OHT group, or (2) have been diagnosed of POAG such as the POAG group. Participants were interviewed for obtaining sociodemographic and personal/familial records, clinically examined, and their tear samples were collected and frozen at 80 °C until processing for molecular-genetic assays. Tear RNA extraction, libraries construction, and next generation sequencing were performed. Here, we demonstrated, for the first time, the differential expression profiling of eight miRNAs when comparing tears from the OHT versus the POAG groups: the miR-26b-5p, miR-152-3p, miR-30e-5p, miR-125b-2-5p, miR-224-5p, miR-151a-3p, miR-1307-3p, and the miR-27a-3p. Gene information was set up from the DIANA-TarBase v7, DIANA-microT-CDS, and TargetScan v7.1 databases. To build a network of metabolic pathways, only genes appearing in at least four of the following databases: DisGeNet, GeneDistiller, MalaCards, OMIM PCAN, UniProt, and GO were considered. We propose miRNAs and their target genes/signaling pathways as candidates for a better understanding of the molecular-genetic bases of glaucoma and, in this way, to gain knowledge to achieve optimal diagnosis strategies for properly identifying HTO at higher risk of glaucoma ND. Further research is needed to validate these miRNAs to discern the potential role as biomarkers involved in oxidative stress, immune response, and apoptosis for the diagnosis and/or prognosis of OHT and the prevention of glaucoma ND.https://www.mdpi.com/2077-0383/10/11/2227ocular hypertensionglaucomatearsmiRNAsnext generation sequencingbiomarkers |
spellingShingle | Jorge Raga-Cervera Jose M. Bolarin Jose M. Millan Jose J. Garcia-Medina Laia Pedrola Javier Abellán-Abenza Mar Valero-Vello Silvia M. Sanz-González José E. O’Connor David Galarreta-Mira Elena Bendala-Tufanisco Aloma Mayordomo-Febrer Maria D. Pinazo-Durán Vicente Zanón-Moreno miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks Journal of Clinical Medicine ocular hypertension glaucoma tears miRNAs next generation sequencing biomarkers |
title | miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks |
title_full | miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks |
title_fullStr | miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks |
title_full_unstemmed | miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks |
title_short | miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks |
title_sort | mirnas and genes involved in the interplay between ocular hypertension and primary open angle glaucoma oxidative stress inflammation and apoptosis networks |
topic | ocular hypertension glaucoma tears miRNAs next generation sequencing biomarkers |
url | https://www.mdpi.com/2077-0383/10/11/2227 |
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