2025
Retinal Pigmented Epithelium and the Outer Blood-Retinal Barrier
Rizzolo L. Retinal Pigmented Epithelium and the Outer Blood-Retinal Barrier. 2025, 587-601. DOI: 10.1016/b978-0-443-13820-1.00020-7.Peer-Reviewed Original ResearchRetinal pigment epitheliumOuter blood-retinal barrierBlood-retinal barrierNeurosensory retinaClaudin-19Pigment epitheliumTight junctionsRetinal pigment epithelium functionHuman retinal pigment epitheliumBarrier functionRetinal barrierCo-culture systemClaudin familyParacellular spaceFamily of transmembrane proteinsEpitheliumChoriocapillarisCo-CultureCapillary bedClaudinRetinaBidirectional interactionsGene expressionPhysiological functionsTransmembrane proteins
2024
A simulacrum of proliferative vitreoretinopathy (PVR): development and proteomics-based validation of an in vitro model
Sharma S, Thakur A, Sharma M, Katoch D, Bansal R, Singh R, Dogra M, Luthra-Guptasarma M. A simulacrum of proliferative vitreoretinopathy (PVR): development and proteomics-based validation of an in vitro model. Journal Of Proteins And Proteomics 2024, 15: 105-118. DOI: 10.1007/s42485-024-00140-0.Peer-Reviewed Original ResearchRetinal pigment epitheliumCell culture-based modelsEpithelial-mesenchymal transitionProliferative vitreoretinopathyCell epithelial-mesenchymal transitionEpiretinal membraneRetinal detachmentCulture-based modelsRetinal pigment epithelium cellsVitreous humorRetinal reattachment surgeryTractional retinal detachmentBlood-retinal barrierAssociated with epithelial-mesenchymal transitionExpression of fibronectinOccurrence of epithelial-mesenchymal transitionTesting of therapeuticsSubretinal fluidReattachment surgeryOcular traumaIn vitro modelPigment epitheliumVision lossDisease progressionExtracellular matrix
2023
Chemiexcitation and melanin in photoreceptor disc turnover and prevention of macular degeneration
Lyu Y, Tschulakow A, Wang K, Brash D, Schraermeyer U. Chemiexcitation and melanin in photoreceptor disc turnover and prevention of macular degeneration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2216935120. PMID: 37155898, PMCID: PMC10194005, DOI: 10.1073/pnas.2216935120.Peer-Reviewed Original ResearchConceptsRetinal pigment epitheliumIntravitreal injectionMacular degenerationMelanolipofuscin granulesLipofuscin accumulationAge-related macular degenerationAlbino micePigmented miceMouse modelStargardt diseasePigment epitheliumRetinal pathologyRetinal degenerationNitric oxideDegenerationMiceLipofuscinPigment lipofuscinPhotoreceptor disksAlbinoAccelerated accumulationInjectionDiseasePathologyInflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration in Mertk-associated retinitis pigmentosa
Mercau M, Akalu Y, Mazzoni F, Gyimesi G, Alberto E, Kong Y, Hafler B, Finnemann S, Rothlin C, Ghosh S. Inflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration in Mertk-associated retinitis pigmentosa. Science Advances 2023, 9: eade9459. PMID: 36662852, PMCID: PMC9858494, DOI: 10.1126/sciadv.ade9459.Peer-Reviewed Original ResearchConceptsRetinal pigment epitheliumEarly-onset photoreceptor degenerationPR degenerationPigment epitheliumPhotoreceptor degenerationMERTK-associated retinitis pigmentosaJAK1/2 inhibitor ruxolitinibMicroglia activationMonocyte infiltrationInhibitor ruxolitinibMouse modelInflammationLoss of functionDefective phagocytosisInflammation drivesRetinitis pigmentosaDegenerationHypomorphic expressionMiceEpitheliumPhagocytosisRuxolitinibPigmentosaSeverity
2022
Tissue-specific modifier alleles determine Mertk loss-of-function traits
Akalu YT, Mercau ME, Ansems M, Hughes LD, Nevin J, Alberto EJ, Liu XN, He LZ, Alvarado D, Keler T, Kong Y, Philbrick WM, Bosenberg M, Finnemann SC, Iavarone A, Lasorella A, Rothlin CV, Ghosh S. Tissue-specific modifier alleles determine Mertk loss-of-function traits. ELife 2022, 11: e80530. PMID: 35969037, PMCID: PMC9433089, DOI: 10.7554/elife.80530.Peer-Reviewed Original ResearchConceptsAnti-tumor immunityKO miceRetinal pigment epitheliumRetinal degenerationPigment epitheliumPro-inflammatory tumor microenvironmentSyngeneic mouse tumor modelsKO mice displayEarly-onset retinal degenerationSevere retinal degenerationMouse tumor modelsFailure of macrophagesKnockout mouse modelPhotoreceptor outer segmentsMouse modelMice displayTumor modelTumor microenvironmentMacrophage phagocytosisReceptor tyrosine kinasesMiceCritical roleDegenerationMerTKImmunity
2021
Altered transcriptome and disease-related phenotype emerge only after fibroblasts harvested from patients with age-related macular degeneration are differentiated into retinal pigment epithelium
Cai H, Gong J, Team N, Noggle S, Paull D, Rizzolo LJ, Del Priore LV, Fields MA. Altered transcriptome and disease-related phenotype emerge only after fibroblasts harvested from patients with age-related macular degeneration are differentiated into retinal pigment epithelium. Experimental Eye Research 2021, 207: 108576. PMID: 33895162, DOI: 10.1016/j.exer.2021.108576.Peer-Reviewed Original ResearchConceptsAge-related macular degenerationRetinal pigment epitheliumMacular degenerationPigment epitheliumInduced pluripotent stem cellsEtiology of AMDMitochondrial dysfunctionAge-matched controlsNovel therapeutic targetTranscriptome of fibroblastsAMD patientsNormal donorsFibroblasts of patientsTherapeutic targetPatientsMore studiesAltered transcriptomeDisease phenotypeSignificant differencesCell linesMitochondrial functionDysfunctionOriginal fibroblastsDistinct transcriptomesDegenerationChoroidal congestion mouse model: Could it serve as a pachychoroid model?
Matsumoto H, Mukai R, Hoshino J, Oda M, Matsuzaki T, Ishizaki Y, Shibasaki K, Akiyama H. Choroidal congestion mouse model: Could it serve as a pachychoroid model? PLOS ONE 2021, 16: e0246115. PMID: 33507997, PMCID: PMC7843010, DOI: 10.1371/journal.pone.0246115.Peer-Reviewed Original ResearchConceptsPachychoroid spectrum diseasesRetinal pigment epitheliumVortex vein congestionVortex veinsSpectrum diseaseChoroidal vesselsUltra-widefield indocyanine green angiographyDilated outer choroidal vesselsDilation of choroidal vesselsMouse modelRPE flatmountsVein congestionDilated vortex veinsOuter choroidal vesselsIndocyanine green angiographyInflammatory response-related genesWild type miceOptical coherence tomographyTissue sectionsDay 7 groupChoroidal congestionChoroidal thickeningPachychoroid featuresRPE degenerationMacular disorders
2020
Partially Differentiated Neuroretinal Cells Promote Maturation of the Retinal Pigment Epithelium
Singh D, Chen X, Xia T, Ghiassi-Nejad M, Tainsh L, Adelman RA, Rizzolo LJ. Partially Differentiated Neuroretinal Cells Promote Maturation of the Retinal Pigment Epithelium. Investigative Ophthalmology & Visual Science 2020, 61: 9-9. PMID: 33151282, PMCID: PMC7671856, DOI: 10.1167/iovs.61.13.9.Peer-Reviewed Original ResearchConceptsRetinal pigment epitheliumRetinal progenitor cellsTransepithelial electrical resistanceNeurosensory retinaPigment epitheliumHuman fetal retinal pigment epitheliumRecoverin-positive cellsFetal retinal pigment epitheliumGanglion cell layerAbility of RPERPE signature genesRed/green opsinTranswell filter insertsStem cellsQuantitative RT-PCRGlial markersHuman stem cellsExpression of rhodopsinInterneuron markersBipolar cellsRetinal culturesRetinaRT-PCRProgenitor cellsPresumptive photoreceptorsShootin‐1 is required for nervous system development in zebrafish
Emerson S, Stergas H, Bupp‐Chickering S, Ebert A. Shootin‐1 is required for nervous system development in zebrafish. Developmental Dynamics 2020, 249: 1285-1295. PMID: 32406957, DOI: 10.1002/dvdy.194.Peer-Reviewed Original ResearchConceptsNervous system developmentLoss of repressionShootin-1Peripheral nervous systemRepulsive axon guidance cuesDownstream signaling mechanismsPhenotypic consequencesNervous systemAxon guidance cuesNeuronal polarityPatterning defectsMicroarray screeningRetinal pigment epitheliumCell migrationGuidance cuesSignaling mechanismsFunctional roleImpaired migrationPLXNA2RepressionPigment epitheliumOptic vesiclePathfinding errorsZebrafishRegulationUnstimulated, Serum-free Cultures of Retinal Pigment Epithelium Excrete Large Mounds of Drusen-like Deposits
Chen X, Singh D, Adelman RA, Rizzolo LJ. Unstimulated, Serum-free Cultures of Retinal Pigment Epithelium Excrete Large Mounds of Drusen-like Deposits. Current Eye Research 2020, 45: 1390-1394. PMID: 32202447, DOI: 10.1080/02713683.2020.1740744.Peer-Reviewed Original ResearchMeSH KeywordsActinsApolipoproteins ECalciumCell Culture TechniquesCell LineCell ProliferationCoculture TechniquesCulture Media, Serum-FreeElectric ImpedanceHumansInduced Pluripotent Stem CellsLipid MetabolismRetinal DrusenRetinal Pigment EpitheliumStem CellsTight JunctionsTissue Inhibitor of Metalloproteinase-3VitronectinConceptsRetinal pigment epitheliumLong-term Natural History of Atrophy in Eyes with Choroideremia—A Systematic Review and Meta-analysis of Individual-Level Data
Shen LL, Ahluwalia A, Sun M, Young BK, Grossetta Nardini HK, Del Priore LV. Long-term Natural History of Atrophy in Eyes with Choroideremia—A Systematic Review and Meta-analysis of Individual-Level Data. Ophthalmology Retina 2020, 4: 840-852. PMID: 32362554, PMCID: PMC7415675, DOI: 10.1016/j.oret.2020.03.003.Peer-Reviewed Original ResearchConceptsResidual retinal pigment epitheliumLong-term natural historyHorizontal translation factorFundus autofluorescenceRPE areaNatural historyUntreated eyesSystematic reviewPrognosis Studies toolRisk of biasRetinal pigment epitheliumLog-transformed areaAnatomic endpointsPatient ageRPE changesTreatment trialsDisease progressionAnatomic measuresPigment epitheliumMeta-analysisLiterature databasesIndividual eyesCross-sectional dataChoroideremiaAtrophyMycobacterium Tuberculosis Modulates Fibroblast Growth Factor and Vascular Endothelial Growth Factor in Ocular Tuberculosis
Singh N, Singh R, Sharma R, Kumar A, Sharma S, Agarwal A, Gupta V, Singh R, Katoch D. Mycobacterium Tuberculosis Modulates Fibroblast Growth Factor and Vascular Endothelial Growth Factor in Ocular Tuberculosis. Ocular Immunology And Inflammation 2020, 29: 1445-1451. PMID: 32160084, DOI: 10.1080/09273948.2020.1734212.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorRetinal pigment epitheliumAngiogenesis growth factorsEndothelial growth factorFibroblast growth factorGrowth factorTear samplesPattern of vascular endothelial growth factorPaucibacillary conditionOcular tuberculosisRetina clinicIntraocular tuberculosisAngiogenic growth factorsRPE cellsPigment epitheliumVitreous fluidFlow cytometryConcomitant surgeMtb bacilliCulture supernatantsVitreousPatientsMtbPathogenesisTuberculosis
2019
Stem cell-derived retinal pigment epithelium from patients with age-related macular degeneration exhibit reduced metabolism and matrix interactions
Gong J, Cai H, Team N, Noggle S, Paull D, Rizzolo LJ, Del Priore LV, Fields MA. Stem cell-derived retinal pigment epithelium from patients with age-related macular degeneration exhibit reduced metabolism and matrix interactions. Stem Cells Translational Medicine 2019, 9: 364-376. PMID: 31840941, PMCID: PMC7031648, DOI: 10.1002/sctm.19-0321.Peer-Reviewed Original ResearchConceptsExtracellular matrixIPSC-RPEMetabolic-related pathwaysComplement immune systemTransepithelial electrical resistanceRod photoreceptor outer segmentsPluripotent stem cellsAged Bruch's membraneCell-specific morphologyObserved phenotypeAltered extracellular matrixControl iPSCsMitochondrial respirationMitochondrial functionMatrix interactionsCell attachmentStem cellsTranscriptomePhotoreceptor outer segmentsDistinct clustersComplement genesRetinal pigment epitheliumGenesIPSCsMembraneDisease-associated mutations of claudin-19 disrupt retinal neurogenesis and visual function
Wang SB, Xu T, Peng S, Singh D, Ghiassi-Nejad M, Adelman RA, Rizzolo LJ. Disease-associated mutations of claudin-19 disrupt retinal neurogenesis and visual function. Communications Biology 2019, 2: 113. PMID: 30937396, PMCID: PMC6433901, DOI: 10.1038/s42003-019-0355-0.Peer-Reviewed Original ResearchConceptsRetinal pigment epitheliumClaudin-19Retinal neurogenesisP1 waveOuter nuclear layerRPE signature genesARPE19 cell lineOcular involvementKidney diseaseVisual functionFamilial hypomagnesaemiaNuclear layerBipolar cellsNewborn miceOcular diseasesPigment epitheliumRetinal isomeraseDiseaseMiceHuman induced pluripotent cellsRetinal differentiationSignature genesCell linesNeurogenesisInduced pluripotent cellsAn ABCA4 loss-of-function mutation causes a canine form of Stargardt disease
Mäkeläinen S, Gòdia M, Hellsand M, Viluma A, Hahn D, Makdoumi K, Zeiss CJ, Mellersh C, Ricketts SL, Narfström K, Hallböök F, Ekesten B, Andersson G, Bergström TF. An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease. PLOS Genetics 2019, 15: e1007873. PMID: 30889179, PMCID: PMC6424408, DOI: 10.1371/journal.pgen.1007873.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsATP Binding Cassette Transporter, Subfamily A, Member 4ATP-Binding Cassette TransportersBase SequenceCodon, NonsenseDisease Models, AnimalDog DiseasesDogsFemaleGenes, RecessiveHomozygoteHumansLipofuscinMacular DegenerationMaleMicroscopy, FluorescenceModels, MolecularMutagenesis, InsertionalMutationPedigreeProtein ConformationRetinaStargardt DiseaseWhole Genome SequencingConceptsRetinal pigment epitheliumStargardt diseaseAutosomal recessive retinal degenerative diseaseRetinal degenerationABCA4 geneVisual impairmentCentral visual impairmentFull-length ABCA4 proteinFunction mutationsLabrador Retriever dogsLarge animal modelRetinal degenerative diseasesAutosomal recessive retinal degenerationMember 4 geneRecessive retinal degenerationStandard treatmentClinical trialsClinical signsLipofuscin depositsPigment epitheliumAnimal modelsCanine modelUnaffected dogsAffected dogsCone photoreceptors
2018
The Zinc-Metallothionein Redox System Reduces Oxidative Stress in Retinal Pigment Epithelial Cells
Rodríguez-Menéndez S, García M, Fernández B, Álvarez L, Fernández-Vega-Cueto A, Coca-Prados M, Pereiro R, González-Iglesias H. The Zinc-Metallothionein Redox System Reduces Oxidative Stress in Retinal Pigment Epithelial Cells. Nutrients 2018, 10: 1874. PMID: 30513827, PMCID: PMC6315569, DOI: 10.3390/nu10121874.Peer-Reviewed Original ResearchConceptsRetinal pigment epitheliumOxidative stressRetinal pigment epithelial cellsOxidative damagePre-treated cellsInduces oxidative stressPigment epithelial cellsNon-treated cellsReactive oxygen intermediatesΜM of zincPigment epitheliumRPE cellsZn-MTProtective mechanismEpithelial cellsFree radical generatorMT levelsAAPH treatmentOxygen intermediatesRetinal pigment epithelium aperture: A late-onset complication in adult-onset foveomacular vitelliform dystrophy
Bansal R, Yangzes S, Singh R, Katoch D, Dogra M, Gupta V, Gupta A. Retinal pigment epithelium aperture: A late-onset complication in adult-onset foveomacular vitelliform dystrophy. Indian Journal Of Ophthalmology 2018, 66: 83-88. PMID: 29283129, PMCID: PMC5778589, DOI: 10.4103/ijo.ijo_676_17.Peer-Reviewed Original ResearchConceptsAdult-onset foveomacular vitelliform dystrophyNatural courseVitelliform dystrophyVitelliform materialVitelliruptive stageCases of adult-onset foveomacular vitelliform dystrophySpectral domain-optical coherence tomographyRetinal pigment epitheliumLate-onset complicationsRecords of clinical examinationFundus autofluorescenceFluorescein angiographyPigment epitheliumClinical examinationCoherence tomographyDiagnosed casesComplicationsDystrophyVitelliformAngiographyFundusEpitheliumPatientsTomographyDisease
2017
A biodegradable scaffold enhances differentiation of embryonic stem cells into a thick sheet of retinal cells
Singh D, Wang SB, Xia T, Tainsh L, Ghiassi-Nejad M, Xu T, Peng S, Adelman RA, Rizzolo LJ. A biodegradable scaffold enhances differentiation of embryonic stem cells into a thick sheet of retinal cells. Biomaterials 2017, 154: 158-168. PMID: 29128844, DOI: 10.1016/j.biomaterials.2017.10.052.Peer-Reviewed Original ResearchConceptsRetinal degenerationNeurosensory retinaRetinal cellsHost retinal pigment epitheliumStem cellsOuter nuclear layerRetinal pigment epitheliumRetinal cell typesElaborate arborsQuantitative RT-PCRLeading causeImmune responseNuclear layerMouse modelPigment epitheliumSubretinal spaceForebrain cellsMinimal immune responseTherapeutic agentsRetinal laminationRT-PCRDegenerationRetinaRetinal organoidsConfocal immunocytochemistryQuantitative study of zinc and metallothioneins in the human retina and RPE cells by mass spectrometry-based methodologies
Rodríguez-Menéndez S, Fernández B, García M, Álvarez L, Fernández M, Sanz-Medel A, Coca-Prados M, Pereiro R, González-Iglesias H. Quantitative study of zinc and metallothioneins in the human retina and RPE cells by mass spectrometry-based methodologies. Talanta 2017, 178: 222-230. PMID: 29136815, DOI: 10.1016/j.talanta.2017.09.024.Peer-Reviewed Original ResearchEffects of diabetic retinopathy on the barrier functions of the retinal pigment epithelium
Xia T, Rizzolo LJ. Effects of diabetic retinopathy on the barrier functions of the retinal pigment epithelium. Vision Research 2017, 139: 72-81. PMID: 28347688, DOI: 10.1016/j.visres.2017.02.006.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBlood-retinal barrierRetinal pigment epitheliumOuter blood-retinal barrierRPE barrier functionDiabetic retinopathyBarrier functionPigment epitheliumInner blood-retinal barrierEffect of diabetesRetinal endothelial cellsMicrovascular complicationsDiabetes mellitusNeurosensory retinaRetinal healthParacellular spaceRetinopathyMetabolic processingEndothelial cellsEarly effectsDiabetesActive transportTight junctionsCulture modelEpitheliumTransepithelial movement
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