miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks

Fecha de publicación: 01/06/2021 Fecha Ahead of Print: 21/05/2021

Autores de IIS La Fe

José María Millán Salvador

Autor
Laia Pedrola Vidal

Autor

Participantes ajenos a IIS La Fe

Raga-Cervera, J
Bolarin, JM
Garcia-Medina, JJ
Abellan-Abenza, J
Valero-Vello, M
Sanz-Gonzalez, SM
O'Connor, JE
Galarreta-Mira, D
Bendala-Tufanisco, E
Mayordomo-Febrer, A
Pinazo-Duran, MD
Zanon-Moreno, V

Grupos

Abstract

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 degrees 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.

Datos de la publicación

ISSN/ISSNe:: 2077-0383, 2077-0383
Tipo:: Article
Páginas:: -
DOI:: 10.3390/jcm10112227
Factor de Impacto:: 1,040 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

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Métricas

Filiaciones

Raga-Cervera, J:: Hosp Manises, Valencia 46940, Spain
Bolarin, JM:: Technol Ctr Informat & Commun Technol CENTIC, Murcia 30100, Spain
Millan, JM:: Univ & Polytech Hosp La Fe, Sequencing Serv, Valencia 46026, Spain
Garcia-Medina, JJ:: FISABIO, Ophthalm Res Unit Santiago Grisolia, Valencia 46017, Spain

Gen Univ Hosp Morales Meseguer, Dept Ophthalmol, Murcia 30007, Spain

Univ Murcia, Dept Ophthalmol & Optometry, Murcia 30120, Spain

Inst Hlth Carlos III, Spanish Net Ophthalm Res OFTARED RD16 0008 0022, Madrid 28029, Spain
Pedrola, L:: Univ & Polytech Hosp La Fe, Sequencing Serv, Valencia 46026, Spain
Abellan-Abenza, J:: Technol Ctr Informat & Commun Technol CENTIC, Murcia 30100, Spain
Valero-Vello, M:: FISABIO, Ophthalm Res Unit Santiago Grisolia, Valencia 46017, Spain
Sanz-Gonzalez, SM:: FISABIO, Ophthalm Res Unit Santiago Grisolia, Valencia 46017, Spain

Inst Hlth Carlos III, Spanish Net Ophthalm Res OFTARED RD16 0008 0022, Madrid 28029, Spain

Univ Valencia, Fac Med & Odontol, Dept Surg, Cellular & Mol Ophthalmobiol Grp, Valencia 46010, Spain
O'Connor, JE:: Joint Res Unit Principe Felipe Res Ctr & Univ Val, Lab Cyt, Valencia 46010, Spain
Galarreta-Mira, D:: Univ Clin Hosp Valladolid, Valladolid 47003, Spain
Bendala-Tufanisco, E:: Inst Hlth Carlos III, Spanish Net Ophthalm Res OFTARED RD16 0008 0022, Madrid 28029, Spain

Mixed Res Unit Visual Hlth & Vet Ophthalmol CEU F, Valencia 46020, Spain

CEU Univ, Fac Hlth Sci, Dept Physiol, Valencia 46115, Spain
Mayordomo-Febrer, A:: Inst Hlth Carlos III, Spanish Net Ophthalm Res OFTARED RD16 0008 0022, Madrid 28029, Spain

Mixed Res Unit Visual Hlth & Vet Ophthalmol CEU F, Valencia 46020, Spain

CEU Univ, Fac Vet Med, Anim Med & Surg Dept, Valencia 46115, Spain
Pinazo-Duran, MD:: FISABIO, Ophthalm Res Unit Santiago Grisolia, Valencia 46017, Spain

Inst Hlth Carlos III, Spanish Net Ophthalm Res OFTARED RD16 0008 0022, Madrid 28029, Spain

Univ Valencia, Fac Med & Odontol, Dept Surg, Cellular & Mol Ophthalmobiol Grp, Valencia 46010, Spain
Zanon-Moreno, V:: FISABIO, Ophthalm Res Unit Santiago Grisolia, Valencia 46017, Spain

Inst Hlth Carlos III, Spanish Net Ophthalm Res OFTARED RD16 0008 0022, Madrid 28029, Spain

Valencian Int Univ, Fac Hlth Sci, Valencia 46002, Spain

Keywords

ocular hypertension; glaucoma; tears; miRNAs; next generation sequencing; biomarkers; genes; signaling pathways; oxidative stress; inflammation; apoptosis; neurodegeneration

Campos de estudio

Financiación

Institute of Health Carlos III

Rare Diseases Networking Biomedical Research Center

Spanish Glaucoma Association

VLC-Biomed GLAUMIRNA project

Proyectos asociados

CARACTERIZACION MOLECULAR DE PACIENTES CON SINDROME DE USHER. ESTUDIO DE LOS GENES RESPONSABLES: CDH23 Y PCDH15 Y CANDIDATOS: WHRN, CXADR Y PDZK7

Investigador Principal: JOSÉ MARÍA MILLÁN SALVADOR

PI07/0558 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2008

MOLECULAR MAECHANISMS OF RETINAL DEGENERATION IN HUMANS WITH RETINITIS PIGMENTOSA. ROLE OF INFLAMMATION, OXIDATIVE STRESS AND GLIAL ACTIVATION

CP09/00118 (MIGUEL SERVET) . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

RED DE BIOBANCOS (BIOBANCOS)

RD09/0076/00021 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

CARACTERIZACION MOLECULAR EN PACIENTES CON SINDROME DE USHER TIPO I MEDIANTE LA APLICACION DE LAS TECNICAS DE SECUENCIACION Y CGH-ARRAY EN GENES RESPONSABLES Y GENES CANDIDATOS

FPU_AP2009-3344 . MINISTERIO DE EDUCACION, CULTURA Y DEPORTE; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010