2022
Retinal Cell Transplantation, Biomaterials, and In Vitro Models for Developing Next-generation Therapies of Age-related Macular Degeneration
Rizzolo LJ, Nasonkin IO, Adelman RA. Retinal Cell Transplantation, Biomaterials, and In Vitro Models for Developing Next-generation Therapies of Age-related Macular Degeneration. Stem Cells Translational Medicine 2022, 11: 269-281. PMID: 35356975, PMCID: PMC8968686, DOI: 10.1093/stcltm/szac001.Peer-Reviewed Original ResearchMeSH KeywordsBiocompatible MaterialsCell TransplantationHumansMacular DegenerationRetinaRetinal Pigment EpitheliumConceptsAge-related macular degenerationMacular degenerationPathology of AMDOuter blood-retinal barrierBlood-retinal barrierRetinal pigment epithelium cellsRetinal degenerative conditionsRisky surgical procedureCell replacement mechanismLoss of photoreceptorsRetinal cell transplantationPigment epithelium cellsCell therapy approachesRPE patchesNext-generation therapiesTransplant proceduresCell transplantationRPE transplantsClinical trialsSurgical proceduresApical processesBasal sideDegenerative conditionsRPE apical processesSevere impairment
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 transcriptomesDegenerationKnockdown of Claudin-19 in the Retinal Pigment Epithelium Is Accompanied by Slowed Phagocytosis and Increased Expression of SQSTM1
Liu F, Peng S, Adelman RA, Rizzolo LJ. Knockdown of Claudin-19 in the Retinal Pigment Epithelium Is Accompanied by Slowed Phagocytosis and Increased Expression of SQSTM1. Investigative Ophthalmology & Visual Science 2021, 62: 14-14. PMID: 33591357, PMCID: PMC7900869, DOI: 10.1167/iovs.62.2.14.Peer-Reviewed Original ResearchConceptsSequestosome 1/p62Photoreceptor outer segmentsInternalized photoreceptor outer segmentsOxidative stress responseApical junctional complexActivation of AMPKTransepithelial electrical resistanceFluorescence-activated cell sortingWestern blottingClaudin-19Expression of proteinsSteady-state levelsProtein kinaseFilamentous actinEffect of AMPStress responseQuantitative RT-PCRKnockdownPOS degradationAMPKJunctional complexesEnzymatic activityCell sortingExpression of metallothioneinProteasome inhibitors
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 photoreceptorsClaudins regulate gene and protein expression of the retinal pigment epithelium independent of their association with tight junctions
Liu F, Xu T, Peng S, Adelman RA, Rizzolo LJ. Claudins regulate gene and protein expression of the retinal pigment epithelium independent of their association with tight junctions. Experimental Eye Research 2020, 198: 108157. PMID: 32712183, DOI: 10.1016/j.exer.2020.108157.Peer-Reviewed Original ResearchMeSH KeywordsBlotting, WesternCells, CulturedClaudinsGene ExpressionHumansMembrane ProteinsRetinal Pigment EpitheliumRNA, MessengerTight JunctionsUnstimulated, 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 epithelium
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 ResearchMeSH KeywordsBruch MembraneHumansInduced Pluripotent Stem CellsMacular DegenerationRetinal Pigment EpitheliumConceptsExtracellular 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 epitheliumGenesIPSCsMembraneInteractions of the choroid, Bruch's membrane, retinal pigment epithelium, and neurosensory retina collaborate to form the outer blood-retinal-barrier
Fields M, Del Priore LV, Adelman RA, Rizzolo LJ. Interactions of the choroid, Bruch's membrane, retinal pigment epithelium, and neurosensory retina collaborate to form the outer blood-retinal-barrier. Progress In Retinal And Eye Research 2019, 76: 100803. PMID: 31704339, DOI: 10.1016/j.preteyeres.2019.100803.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsDisease-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 cells
2017
Effects 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 StatementsMeSH KeywordsAnimalsBlood-Retinal BarrierCapillary PermeabilityDiabetic RetinopathyHumansRetinal Pigment EpitheliumTight JunctionsConceptsBlood-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
2016
Claudin-3 and claudin-19 partially restore native phenotype to ARPE-19 cells via effects on tight junctions and gene expression
Peng S, Wang SB, Singh D, Zhao PY, Davis K, Chen B, Adelman RA, Rizzolo LJ. Claudin-3 and claudin-19 partially restore native phenotype to ARPE-19 cells via effects on tight junctions and gene expression. Experimental Eye Research 2016, 151: 179-189. PMID: 27593915, DOI: 10.1016/j.exer.2016.08.021.Peer-Reviewed Original Research
2015
Human Adult Retinal Pigment Epithelial Stem Cell–Derived RPE Monolayers Exhibit Key Physiological Characteristics of Native TissuePhysiology of Cultured Adult Human RPE
Blenkinsop TA, Saini JS, Maminishkis A, Bharti K, Wan Q, Banzon T, Lotfi M, Davis J, Singh D, Rizzolo LJ, Miller S, Temple S, Stern JH. Human Adult Retinal Pigment Epithelial Stem Cell–Derived RPE Monolayers Exhibit Key Physiological Characteristics of Native TissuePhysiology of Cultured Adult Human RPE. Investigative Ophthalmology & Visual Science 2015, 56: 7085-7099. PMID: 26540654, PMCID: PMC4640474, DOI: 10.1167/iovs.14-16246.Peer-Reviewed Original ResearchTRP Channels Localize to Subdomains of the Apical Plasma Membrane in Human Fetal Retinal Pigment EpitheliumTRP Channels of Human Fetal RPE
Zhao PY, Gan G, Peng S, Wang SB, Chen B, Adelman RA, Rizzolo LJ. TRP Channels Localize to Subdomains of the Apical Plasma Membrane in Human Fetal Retinal Pigment EpitheliumTRP Channels of Human Fetal RPE. Investigative Ophthalmology & Visual Science 2015, 56: 1916-1923. PMID: 25736794, PMCID: PMC4364639, DOI: 10.1167/iovs.14-15738.Peer-Reviewed Original ResearchConceptsHuman fetal RPETRP channelsApical membraneFetal RPEApical plasma membraneCell-cell contactTransepithelial electrical resistanceTransient receptor potential channelsTight junctionsSubcellular localizationInhibitor of calpainPrimary ciliaRT-PCRPlasma membraneBasal channel activityQuantitative RT-PCRApical tight junctionsExpression of TRPC4Ion channelsBasolateral surfaceApical microvilliApical surfaceChannel activityConfocal microscopyTRPM3
2014
Barrier properties of cultured retinal pigment epithelium
Rizzolo LJ. Barrier properties of cultured retinal pigment epithelium. Experimental Eye Research 2014, 126: 16-26. PMID: 24731966, DOI: 10.1016/j.exer.2013.12.018.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2013
Engineering a Blood-Retinal Barrier With Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium: Transcriptome and Functional Analysis
Peng S, Gan G, Qiu C, Zhong M, An H, Adelman RA, Rizzolo LJ. Engineering a Blood-Retinal Barrier With Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium: Transcriptome and Functional Analysis. Stem Cells Translational Medicine 2013, 2: 534-544. PMID: 23734062, PMCID: PMC3697821, DOI: 10.5966/sctm.2012-0134.Peer-Reviewed Original ResearchConceptsRetinal pigment epitheliumBlood-retinal barrierHuman retinal pigment epitheliumPigment epitheliumHuman fetal retinal pigment epitheliumOuter blood-retinal barrierTight junctionsFetal retinal pigment epitheliumEmbryonic stem cell-derived retinal pigment epitheliumAdult retinal pigment epitheliumQuantitative reverse transcription polymerase chain reactionMaturation of hESCReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionHuman embryonic stem cell-derived retinal pigment epitheliumStem cell-derived retinal pigment epitheliumRPE replacement therapyPanel of genesReplacement therapyAnimal modelsHuman embryonic stem cellsRetinal degenerationRPE functionSerum-free mediumHuman retina
2012
Effects of Proinflammatory Cytokines on the Claudin-19 Rich Tight Junctions of Human Retinal Pigment EpitheliumCytokine Effects on RPE Tight Junctions
Peng S, Gan G, Rao VS, Adelman RA, Rizzolo LJ. Effects of Proinflammatory Cytokines on the Claudin-19 Rich Tight Junctions of Human Retinal Pigment EpitheliumCytokine Effects on RPE Tight Junctions. Investigative Ophthalmology & Visual Science 2012, 53: 5016-5028. PMID: 22761260, PMCID: PMC3410691, DOI: 10.1167/iovs.11-8311.Peer-Reviewed Original ResearchConceptsHuman fetal RPEEffects of TNFαTransepithelial electrical resistanceProinflammatory cytokinesClaudin-19Tight junctionsAge-related macular degenerationZO-1Effects of cytokinesApical sideSubclinical inflammationTumor necrosisMacular degenerationTNFα receptorsOcular diseasesTNFαSerum-free mediumClaudin-3RPE tight junctionsFetal RPECytokinesClaudin-2Confocal immunofluorescence microscopyInhibitor of apoptosis
2011
Integration of tight junctions and claudins with the barrier functions of the retinal pigment epithelium
Rizzolo LJ, Peng S, Luo Y, Xiao W. Integration of tight junctions and claudins with the barrier functions of the retinal pigment epithelium. Progress In Retinal And Eye Research 2011, 30: 296-323. PMID: 21704180, DOI: 10.1016/j.preteyeres.2011.06.002.Peer-Reviewed Original ResearchConceptsRetinal pigment epitheliumOuter retinaPigment epitheliumTight junctionsBarrier functionOuter blood-retinal barrierBlood-retinal barrierHuman retinal pigment epitheliumBlood-tissue barriersTight junctional proteinsPhotoreceptor layerNeural retinaMetabolic alterationsRetinaEpitheliumClaudin compositionTransepithelial diffusionStem cellsJunctional proteinsClaudinsClaudin-19 and the Barrier Properties of the Human Retinal Pigment Epithelium
Peng S, Rao VS, Adelman RA, Rizzolo LJ. Claudin-19 and the Barrier Properties of the Human Retinal Pigment Epithelium. Investigative Ophthalmology & Visual Science 2011, 52: 1392-1403. PMID: 21071746, PMCID: PMC3101667, DOI: 10.1167/iovs.10-5984.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsCells, CulturedClaudinsElectric ImpedanceFluorescent Antibody Technique, IndirectGene SilencingGestational AgeHumansImmunoblottingMembrane ProteinsOccludinPermeabilityPolyethylene GlycolsRetinal Pigment EpitheliumReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingTight JunctionsConceptsRetinal pigment epitheliumTransepithelial electrical resistanceHuman retinal pigment epitheliumHuman fetal RPECultured human fetal retinal pigment epitheliumPigment epitheliumClaudin-19Retinal sideHuman fetal retinal pigment epitheliumSpread of edemaFetal retinal pigment epitheliumFetal human retinal pigment epitheliumEffect of serumTight junctionsRPE permeabilityQuantitative RT-PCRChoroidal capillariesSubpopulation of cellsClaudin-1RPE barrierClaudin-3RPE tight junctionsRT-PCREpitheliumSerum
2009
Minimal Effects of VEGF and Anti-VEGF Drugs on the Permeability or Selectivity of RPE Tight Junctions
Peng S, Adelman RA, Rizzolo LJ. Minimal Effects of VEGF and Anti-VEGF Drugs on the Permeability or Selectivity of RPE Tight Junctions. Investigative Ophthalmology & Visual Science 2009, 51: 3216-3225. PMID: 20042644, PMCID: PMC2891474, DOI: 10.1167/iovs.09-4162.Peer-Reviewed Original ResearchAngiogenesis InhibitorsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBevacizumabBlood-Retinal BarrierCapillary PermeabilityCells, CulturedClaudinsElectric ImpedanceEnzyme-Linked Immunosorbent AssayFluorescent Antibody Technique, IndirectGene ExpressionHumansImmunoblottingPolyethylene GlycolsPotassiumRanibizumabRetinal Pigment EpitheliumReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSodiumTight JunctionsVascular Endothelial Growth Factor A
2008
Diffusible retinal secretions regulate the expression of tight junctions and other diverse functions of the retinal pigment epithelium.
Sun R, Peng S, Chen X, Zhang H, Rizzolo LJ. Diffusible retinal secretions regulate the expression of tight junctions and other diverse functions of the retinal pigment epithelium. Molecular Vision 2008, 14: 2237-62. PMID: 19057659, PMCID: PMC2593753.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdherens JunctionsAnimalsCell MembraneCells, CulturedChick EmbryoCluster AnalysisCulture Media, ConditionedDiffusionElectric ImpedanceExtracellular MatrixGene Expression ProfilingGene Expression Regulation, DevelopmentalGenomeIon ChannelsKineticsMelaninsMembrane ProteinsMicrotubulesOligonucleotide Array Sequence AnalysisPhagocytosisRetinal Pigment EpitheliumRNA, MessengerSubcellular FractionsTight JunctionsVisual PathwaysConceptsGene expression