2024
The Increased Burden of Rare Variants in Four Matrix Metalloproteinase-Related Genes in Childhood Glaucoma Suggests a Complex Genetic Inheritance of the Disease
Tevar A, Aroca-Aguilar J, Bonet-Fernández J, Atienzar-Aroca R, Campos-Mollo E, Méndez-Hernández C, Morales-Fernández L, Palmer I, Coca-Prados M, Martinez-de-la-Casa J, Garcia-Feijoo J, Escribano J. The Increased Burden of Rare Variants in Four Matrix Metalloproteinase-Related Genes in Childhood Glaucoma Suggests a Complex Genetic Inheritance of the Disease. International Journal Of Molecular Sciences 2024, 25: 5757. PMID: 38891949, PMCID: PMC11171635, DOI: 10.3390/ijms25115757.Peer-Reviewed Original ResearchChildhood glaucomaGene variantsIncreased burden of rare variantsChildhood glaucoma patientsEarly-onset glaucomaIrreversible optic neuropathyAnterior eye chamberRare variantsPartial loss-of-function effectsLoss-of-function effectProportion of rare variantsBurden of rare variantsComplex genetic inheritanceGlaucoma patientsGlaucoma typePrimary glaucomaOptic neuropathyMutational burdenAnterior segmentEndoplasmic reticulum stressEye chamberT cellsHEK 293T cellsGlaucomaNext-generation sequencing
2021
Candidate Glaucoma Biomarkers: From Proteins to Metabolites, and the Pitfalls to Clinical Applications
Cueto A, Álvarez L, García M, Álvarez-Barrios A, Artime E, Cueto L, Coca-Prados M, González-Iglesias H. Candidate Glaucoma Biomarkers: From Proteins to Metabolites, and the Pitfalls to Clinical Applications. Biology 2021, 10: 763. PMID: 34439995, PMCID: PMC8389649, DOI: 10.3390/biology10080763.Peer-Reviewed Original ResearchGlaucoma biomarkersRetinal ganglion cell deathGanglion cell deathProgression of glaucomaExpression of moleculesFuture diagnostic testsHuman eye tissuesOptic nerveSystemic biomarkersHuman glaucomaIntraocular pressureDisease onsetRisk factorsIrreversible blindnessEye diseaseEarly diagnosisGlaucomaPathogenic processesEye tissuesProgressive lossDiagnostic testsNeurodegenerative diseasesBiomarker candidatesMolecular biomarkersBiomarkers
2020
Systemic Alterations of Immune Response-Related Proteins during Glaucoma Development in the Murine Model DBA/2J
Cueto A, Álvarez L, García M, Artime E, Barrios A, Rodríguez-Uña I, Coca-Prados M, González-Iglesias H. Systemic Alterations of Immune Response-Related Proteins during Glaucoma Development in the Murine Model DBA/2J. Diagnostics 2020, 10: 425. PMID: 32585848, PMCID: PMC7345206, DOI: 10.3390/diagnostics10060425.Peer-Reviewed Original ResearchImmune responseSystemic levelsOptic nerve damageImportant molecular changesDiagnosis of glaucomaComplement factor HCandidate molecular biomarkersGlaucomatous miceAdvanced diseaseNerve damageControl miceGlaucoma developmentComplement system proteinsSystemic alterationsDBA/2J miceAnimal modelsComplement C4AFicolin-3Potential biomarkersDifferent experimental groupsEnzyme immunoassayApolipoprotein A4Neurodegenerative diseasesGlaucomaSerum samples
2014
Lysyl Oxidase‐Like 1 gene haplotypes and their association with pseudoexfoliation glaucoma in the Spanish population
ALVAREZ L, GARCIA M, GONZALEZ‐IGLESIAS H, ESCRIBANO J, RODRIGUEZ‐CALVO P, FERNANDEZ‐VEGA L, COCA‐PRADOS M. Lysyl Oxidase‐Like 1 gene haplotypes and their association with pseudoexfoliation glaucoma in the Spanish population. Acta Ophthalmologica 2014, 92: 0-0. DOI: 10.1111/j.1755-3768.2014.t075.x.Peer-Reviewed Original ResearchPseudoexfoliation glaucomaHaploView 4.0 softwareLOXL1 geneCase-control studyUnrelated healthy controlsSpanish populationGenetic variantsXFG patientsCase-control association studyHealthy controlsSpanish patientsAllelic frequency analysisPotential associationCommon genetic variantsLOXL1 SNPsPatientsRisk allelesXFGFragment length polymorphism analysisRestriction fragment length polymorphism analysisNext-generation sequencingGlaucomaGene haplotypesAssociationVariant frequency
2013
Comparative proteomic study in serum of patients with primary open-angle glaucoma and pseudoexfoliation glaucoma
González-Iglesias H, Álvarez L, García M, Escribano J, Rodríguez-Calvo PP, Fernández-Vega L, Coca-Prados M. Comparative proteomic study in serum of patients with primary open-angle glaucoma and pseudoexfoliation glaucoma. Journal Of Proteomics 2013, 98: 65-78. PMID: 24355480, DOI: 10.1016/j.jprot.2013.12.006.Peer-Reviewed Original ResearchConceptsPrimary open-angle glaucomaOpen-angle glaucomaPseudoexfoliation glaucomaGlaucoma patientsInflammatory-related processesSera of patientsForms of glaucomaLarge population studiesPanel of candidatesAge-related blindnessSerum proteinsFunctional pathway analysisClinical manifestationsDietary agentsInflammatory processGlaucoma biomarkersHealthy controlsEarly diagnosisGlaucomaPatientsMajor causeSerumPopulation studiesTwo-dimensional fluorescent difference gel electrophoresisGenetic linkage studiesBicarbonate-Dependent Secretion and Proteolytic Processing of Recombinant Myocilin
Aroca-Aguilar JD, Martínez-Redondo F, Martín-Gil A, Pintor J, Coca-Prados M, Escribano J. Bicarbonate-Dependent Secretion and Proteolytic Processing of Recombinant Myocilin. PLOS ONE 2013, 8: e54385. PMID: 23342144, PMCID: PMC3547000, DOI: 10.1371/journal.pone.0054385.Peer-Reviewed Original ResearchConceptsIrreversible visual lossElevated intraocular pressureIntracellular accumulationC-terminal fragmentVisual lossOptic neuropathyIntraocular pressureIntracellular proteolytic processingProteolytic processingOcular tissuesRecombinant myocilinCalpain IICellular modelMyocilinSecretionPossible factorsExtracellular glycoproteinNeuropathyGlaucoma
2007
Characterization of the Intracellular Proteolytic Cleavage of Myocilin and Identification of Calpain II as a Myocilin-processing Protease*
Sánchez-Sánchez F, Martínez-Redondo F, Aroca-Aguilar JD, Coca-Prados M, Escribano J. Characterization of the Intracellular Proteolytic Cleavage of Myocilin and Identification of Calpain II as a Myocilin-processing Protease*. Journal Of Biological Chemistry 2007, 282: 27810-27824. PMID: 17650508, DOI: 10.1074/jbc.m609608200.Peer-Reviewed Original ResearchConceptsExtracellular calciumCalpain IICalcium-activated proteaseIntraocular pressureT cellsIntracellular proteolytic cleavageCalpain inhibitorsCalcium uptakeProteolytic cleavageCalpain inhibitor IVOlfactomedin-like domainCalpain IInhibitor IVMyocilinEndoplasmic reticulumIntracellular processingLumenRNA interference knockdownCalciumProteolytic processingCellsCulture mediumGlaucomaSubcellular fractionationEndoproteolytic processingRole of MYOC and OPTN sequence variations in Spanish patients with primary open-angle glaucoma.
López-Martínez F, López-Garrido M, Sánchez-Sánchez F, Campos-Mollo E, Coca-Prados M, Escribano J. Role of MYOC and OPTN sequence variations in Spanish patients with primary open-angle glaucoma. Molecular Vision 2007, 13: 862-72. PMID: 17615537, PMCID: PMC2770203.Peer-Reviewed Original ResearchMeSH KeywordsAge of OnsetAmino Acid SequenceCell Cycle ProteinsCell LineCytoskeletal ProteinsExonsEye ProteinsFemaleGene FrequencyGenome, HumanGlaucoma, Open-AngleGlycoproteinsHaplotypesHumansLinkage DisequilibriumMaleMembrane Transport ProteinsMiddle AgedMolecular Sequence DataMutationOcular HypertensionOpen Reading FramesPhenotypePolymorphism, Single-Stranded ConformationalPromoter Regions, GeneticSpainTranscription Factor TFIIIAWhite PeopleConceptsPrimary open-angle glaucomaOcular hypertensionOpen-angle glaucomaPOAG patientsSpanish patientsSequence variationExons of myocilinHeterozygous disease-causing mutationsPathogenic mutationsSingle nucleotide polymorphismsPromoter regionRole of myocilinDNA sequence variationPolymorphic GT microsatelliteCommon single nucleotide polymorphismsPCR-DNA sequencingT cellsComplete coding regionPatientsUnrelated patientsMYOC geneOPTN geneGlaucomaDisease-causing mutationsGT microsatelliteNew perspectives in aqueous humor secretion and in glaucoma: The ciliary body as a multifunctional neuroendocrine gland
Coca-Prados M, Escribano J. New perspectives in aqueous humor secretion and in glaucoma: The ciliary body as a multifunctional neuroendocrine gland. Progress In Retinal And Eye Research 2007, 26: 239-262. PMID: 17321191, DOI: 10.1016/j.preteyeres.2007.01.002.Peer-Reviewed Original ResearchConceptsIntraocular pressureCiliary bodyAqueous humor secretionAqueous humorCiliary epitheliumGlaucoma-associated genesImmune privilege statusDevelopment of glaucomaGlutamate-metabolizing enzymesPathophysiology of glaucomaAnti-angiogenic factorsSteroid-converting enzymesDiurnal circadian rhythmCiliary blood flowOcular ciliary bodyAnterior segmentBlood flowMultifactorial eventGlaucomaNeuroendocrine systemOutflow pathwayEndocrine communicationEndocrine systemEndocrine peptidesRegulatory peptides
2006
Heterozygous CYP1B1 gene mutations in Spanish patients with primary open-angle glaucoma.
López-Garrido MP, Sánchez-Sánchez F, López-Martínez F, Aroca-Aguilar JD, Blanco-Marchite C, Coca-Prados M, Escribano J. Heterozygous CYP1B1 gene mutations in Spanish patients with primary open-angle glaucoma. Molecular Vision 2006, 12: 748-55. PMID: 16862072.Peer-Reviewed Original ResearchMeSH KeywordsAgedAmino Acid SubstitutionAryl Hydrocarbon HydroxylasesCase-Control StudiesConserved SequenceCytochrome P-450 CYP1B1Cytochrome P-450 Enzyme SystemFemaleGene FrequencyGenetic Predisposition to DiseaseGenotypeGlaucoma, Open-AngleHeterozygoteHumansMaleMiddle AgedMutationMutation, MissenseOcular HypertensionPhenotypeSpainConceptsPrimary open-angle glaucomaOcular hypertensionOpen-angle glaucomaCYP1B1 gene mutationsGlaucoma patientsSpanish patientsDevelopment of POAGGene mutationsUnrelated Spanish subjectsOHT subjectsPCR-DNA sequencingPOAG patientsAngle glaucomaPatientsCYP1B1 mutationsGlaucomaSpanish populationSpanish subjectsMissense mutationsDifferent mutationsSignificant changesAmino acid substitutionsSubjectsMutationsAcid substitutions
2005
Myocilin Mutations Causing Glaucoma Inhibit the Intracellular Endoproteolytic Cleavage of Myocilin between Amino Acids Arg226 and Ile227 *
Aroca-Aguilar JD, Sánchez-Sánchez F, Ghosh S, Coca-Prados M, Escribano J. Myocilin Mutations Causing Glaucoma Inhibit the Intracellular Endoproteolytic Cleavage of Myocilin between Amino Acids Arg226 and Ile227 *. Journal Of Biological Chemistry 2005, 280: 21043-21051. PMID: 15795224, DOI: 10.1074/jbc.m501340200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsArginineBlotting, WesternBrefeldin ACattleCell LineComputational BiologyCOS CellsCulture MediaCytoskeletal ProteinsExtracellular Matrix ProteinsEye ProteinsGlaucomaGlycoproteinsGreen Fluorescent ProteinsHumansIsoleucineLeucineMicroscopy, FluorescenceMolecular Sequence DataMutationPeptidesPhenotypeProtein Structure, TertiarySpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationTransfectionConceptsMyocilin mutationPathogenesis of glaucomaCause of blindnessSevere glaucoma phenotypeHuman aqueous humorAqueous humorOcular tissuesGlaucoma phenotypeNonocular tissuesWestern immunoblot analysisGlaucomaPathogenic mutationsOlfactomedin-like domainEndoproteolytic processingWild-type myocilinCell linesImmunoblot analysisMyocilinEndoproteolytic cleavageLeucine zipper-like domainMutant myocilinNormal roleHuman organsInhibitionTissue
2003
Expression of cell surface transmembrane carbonic anhydrase genes CA9 and CA12 in the human eye: overexpression of CA12 (CAXII) in glaucoma
Liao S, Ivanov S, Ivanova A, Ghosh S, Cote M, Keefe K, Coca-Prados M, Stanbridge E, Lerman M. Expression of cell surface transmembrane carbonic anhydrase genes CA9 and CA12 in the human eye: overexpression of CA12 (CAXII) in glaucoma. Journal Of Medical Genetics 2003, 40: 257. PMID: 12676895, PMCID: PMC1735430, DOI: 10.1136/jmg.40.4.257.Peer-Reviewed Original ResearchConceptsNon-pigmented ciliary epithelial cellsGlaucoma patientsEpithelium of corneaNPE cell linesNPE cellsAqueous humor productionCultured NPE cellsGlaucoma eyesIntraocular pressureAqueous humor secretionGlaucomatous eyesCAIX expressionCiliary epithelial cellsCAXII expressionEye donorsCA9 mRNANormal eyesPlasma membrane proteinsEmbryonic eye developmentFundamental physiological processesGlaucoma donorsGlaucomaCiliary epitheliumCAIXEpithelial cells
2002
Adult-Onset Primary Open-Angle Glaucoma Caused by Mutations in Optineurin
Rezaie T, Child A, Hitchings R, Brice G, Miller L, Coca-Prados M, Héon E, Krupin T, Ritch R, Kreutzer D, Crick RP, Sarfarazi M. Adult-Onset Primary Open-Angle Glaucoma Caused by Mutations in Optineurin. Science 2002, 295: 1077-1079. PMID: 11834836, DOI: 10.1126/science.1066901.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlternative SplicingAmino Acid SequenceBrainCell Cycle ProteinsChromosome MappingChromosomes, Human, Pair 10Ciliary BodyExonsEye ProteinsFemaleGlaucoma, Open-AngleGolgi ApparatusHeterozygoteHumansIntraocular PressureMaleMembrane Transport ProteinsMiddle AgedMutationMutation, MissenseNerve Tissue ProteinsOcular HypertensionPedigreePolymorphism, Single-Stranded ConformationalRetinaTrabecular MeshworkTranscription Factor TFIIIAZinc FingersConceptsPrimary open-angle glaucomaHereditary primary open-angle glaucomaNormal intraocular pressureOpen-angle glaucomaAdult-onset primary open-angle glaucomaNeuroprotective roleIntraocular pressureAngle glaucomaTumor necrosisLeading causeTrabecular meshworkOPTN geneCiliary epitheliumCausative genesGlaucomaChromosome 10p14OptineurinSequence alterationsNecrosisRetinaIndividualsBrainEpithelium