2024
Inherited Retinal Degenerations and Non-Neovascular Age-Related Macular Degeneration: Progress and Unmet Needs
Duncan J, Bowman A, Laster A, Gelfman C, Birch D, Boye S, Daiger S, del Priore L, Zack D, Handa J, Board T. Inherited Retinal Degenerations and Non-Neovascular Age-Related Macular Degeneration: Progress and Unmet Needs. Translational Vision Science & Technology 2024, 13: 28. PMID: 39688851, PMCID: PMC11654773, DOI: 10.1167/tvst.13.12.28.Peer-Reviewed Original ResearchConceptsAge-related macular degenerationInherited retinal degenerationNon-neovascular age-related macular degenerationRetinal degenerationGeographic atrophyMacular degenerationDevelopment of treatmentsIrreversible vision lossTherapies to slow progressionNon-neovascularVision lossUnmet needsDegenerationSlow progressionPatientsTreatmentProgressionAtrophyIn the Eyes of the Beholder—New Mertk Knockout Mouse and Re-Evaluation of Phagocytosis versus Anti-Inflammatory Functions of MERTK
Ghosh S, Finnemann S, Vollrath D, Rothlin C. In the Eyes of the Beholder—New Mertk Knockout Mouse and Re-Evaluation of Phagocytosis versus Anti-Inflammatory Functions of MERTK. International Journal Of Molecular Sciences 2024, 25: 5299. PMID: 38791338, PMCID: PMC11121519, DOI: 10.3390/ijms25105299.Peer-Reviewed Original ResearchReceptor tyrosine kinasesFamily of receptor tyrosine kinasesTAM family of receptor tyrosine kinasesEarly-onset photoreceptor degenerationKnockout mouse modelMolecular functionsNegative regulator of inflammationKnockout phenotypesNegative regulatorMouse geneticsRegulation of inflammationMolecular approachesEmbryonic stem cellsAnti-inflammatory functionsRetinal degenerationTyrosine kinasePhotoreceptor degenerationKnockout miceKnockout modelsMouse modelRodent modelsTAM familyMerTK functionStem cellsAlleles
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 accumulationInjectionDiseasePathology
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 roleDegenerationMerTKImmunityPigment epithelium-derived factor engineered to increase glycosaminoglycan affinity while maintaining bioactivity
Chu H, Rebustini I, Becerra S, Wang Y. Pigment epithelium-derived factor engineered to increase glycosaminoglycan affinity while maintaining bioactivity. Biochemical And Biophysical Research Communications 2022, 605: 148-153. PMID: 35334413, PMCID: PMC11371396, DOI: 10.1016/j.bbrc.2022.03.079.Peer-Reviewed Original ResearchConceptsPigment epithelium-derived factorEpithelium-derived factorNegatively charged extracellular matrixInhibit endothelial cell proliferationAmino acid sequenceHyaluronic acidEndothelial cell proliferationExtracellular matrixRetinal degenerationRetinal diseasesRetinal microenvironmentProtect photoreceptorsTherapeutic effectVitreous humorProtein engineeringGlycosaminoglycan affinitySecreted proteinsTherapeutic drugsTube formationTissue homeostasisCell deathCell proliferationEfficient therapeutic drugsCationic residuesBinding assays
2020
Primate model of chronic retinal neovascularization and vascular leakage
Patel C, Goody R, Hu W, Kurian A, James D, Torres R, Christie LA, Hohman T, Lawrence M. Primate model of chronic retinal neovascularization and vascular leakage. Experimental Eye Research 2020, 195: 108031. PMID: 32275921, PMCID: PMC7335215, DOI: 10.1016/j.exer.2020.108031.Peer-Reviewed Original ResearchConceptsGlial fibrillary acidic proteinVascular leakageVon Willebrand factorOptical coherence tomographyFluorescein angiographyRetinal neovascularizationPrimate modelCD105/endoglinNeovascular diseasesRetinal degenerationDL-alpha-aminoadipic acidBilateral intravitreal injectionsInner retinal edemaRetinal vascular leakageRetinal vascular pathologyVascular disease mechanismsColor fundus photographyMüller cell lossFibrillary acidic proteinExpression of vWFAfrican green monkeysCD68 immunoreactivityMacular telangiectasiaRetinal edemaIntravitreal injection
2019
An 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
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 immunocytochemistryLoss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice
Klein ZA, Takahashi H, Ma M, Stagi M, Zhou M, Lam TT, Strittmatter SM. Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice. Neuron 2017, 95: 281-296.e6. PMID: 28728022, PMCID: PMC5558861, DOI: 10.1016/j.neuron.2017.06.026.Peer-Reviewed Original ResearchConceptsLysosomal protein levelsFrontotemporal lobar degenerationProtein levelsMultiple lysosomal enzymesLysosomal enzymesV0 subunitsTMEM106B geneProteomic analysisProgranulin-deficient miceExtent of neurodegenerationCommon neurodegenerative disorderLysosomal acidificationLysosomal enzyme levelsProtein 1Microglial accumulationRisk modificationFTLD riskBehavioral abnormalitiesRetinal degenerationNeurodegenerative disordersFrontotemporal dementiaGRNTMEM106BFunctional relationshipEnzyme levels
2016
Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD)
Fields M, Cai H, Gong J, Del Priore L. Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD). Cells 2016, 5: 44. PMID: 27941641, PMCID: PMC5187528, DOI: 10.3390/cells5040044.Peer-Reviewed Original ResearchInduced pluripotent stem cellsEmbryonic stem cellsAge-related macular degenerationPluripotent stem cellsCell replacement therapyDisease modelingIPSC disease modelingStem cellsReplacement therapyMacular degenerationRegenerative medicineRetinal pigment epithelium cellsStem cell biologyPigment epithelium cellsRetinal degenerative disordersUnlimited sourceDrug development platformClinical trialsDevelopment platformStargardt diseaseAnimal modelsRetinal degenerationAutologous sourceDegenerative disordersTherapeutic useHypomorphic mutations identified in the candidate Leber congenital amaurosis gene CLUAP1
Soens ZT, Li Y, Zhao L, Eblimit A, Dharmat R, Li Y, Chen Y, Naqeeb M, Fajardo N, Lopez I, Sun Z, Koenekoop RK, Chen R. Hypomorphic mutations identified in the candidate Leber congenital amaurosis gene CLUAP1. Genetics In Medicine 2016, 18: 1044-1051. PMID: 26820066, PMCID: PMC4965339, DOI: 10.1038/gim.2015.205.Peer-Reviewed Original ResearchConceptsLeber congenital amaurosisLCA genesRescue experimentsEarly-onset formPhotoreceptor cell deathWhole-exome sequencingDysfunctional photoreceptorsRetinal disease genesCause of diseaseSystemic abnormalitiesLCA cohortMouse retinaRetinal degenerationHypomorphic mutationsCongenital amaurosisLCA patientsCilia-associated genesPhotoreceptor functionProband's mutationCell deathDiseaseProbandsSingle probandHuman diseasesCilia function
2014
Analysis for co-occurring sequence features identifies link between common synonymous variant and an early-terminated NPC1 isoform
Movassagh M, Mudvari P, Kokkinaki M, Edwards N, Golestaneh N, Horvath A. Analysis for co-occurring sequence features identifies link between common synonymous variant and an early-terminated NPC1 isoform. Journal Of Clinical Bioinformatics 2014, 4: 14. DOI: 10.1186/2043-9113-4-14.Peer-Reviewed Original ResearchRetinal pigment epitheliumNPC1 proteinLow-grade brain tumorsVariant nucleotidesFunctional NPC1 proteinTranscriptome-wide searchParallel sequencing technologiesCommon synonymous variantSingle sequencing readExon-intron boundariesDiploid genomeAllelic phaseAlternative splicingHuman transcriptomeSynonymous substitutionsBreast cancerCellular phenotypesBrain tumorsSequencing technologiesPigment epitheliumColon cancerAutosomal recessive mannerCholesterol traffickingRetinal degenerationRNA featuresProgressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice
Hafler BP, Klein ZA, Zhou Z, Strittmatter SM. Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice. Brain Research 2014, 1588: 168-174. PMID: 25234724, PMCID: PMC4254024, DOI: 10.1016/j.brainres.2014.09.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedElectroretinographyGranulinsImmunohistochemistryIntercellular Signaling Peptides and ProteinsMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalNeuronal Ceroid-LipofuscinosesOptical ImagingPhotoreceptor Cells, VertebrateProgranulinsRetinal DegenerationRetinal Ganglion CellsConceptsProgranulin-deficient miceNeuronal ceroid lipofuscinosisAdult-onset neuronal ceroid lipofuscinosisDeficient miceRetinal degenerationCeroid lipofuscinosisRetinal ganglion cellsCentral nervous systemAutofluorescent storage materialMotor dysfunctionNeuropathological analysisGanglion cellsVision lossOptic atrophyEarly deathAutofluorescent lipopigmentsClinical observationsNervous systemDegenerative pathologyMiceDegenerationHomozygous mutationAutofluorescent materialPatientsNeurons
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
The Eye as a Target Organ for Stem Cell Therapy
Fields M, Hwang J, Gong J, Cai H, Del Priore L. The Eye as a Target Organ for Stem Cell Therapy. Stem Cell Biology And Regenerative Medicine 2012, 1-29. DOI: 10.1007/978-1-4614-5493-9_1.Peer-Reviewed Original ResearchAge-related macular degenerationRetinal pigment epitheliumRetinal degenerative diseasesStem cell therapyCell therapyRetinitis pigmentosaDegenerative diseasesCurrent clinical trialsPromising therapeutic optionNature of pathologyViable clinical optionReplacement therapyTherapeutic optionsClinical trialsCell replacement therapyMacular degenerationRetinal disordersCellular disarrayPigment epitheliumTarget organsPharmaceutical treatmentClinical optionProgressive cellular dysfunctionRetinal degenerationTherapeutic interventions
2009
CREB1/ATF1 Activation in Photoreceptor Degeneration and Protection
Beltran WA, Allore HG, Johnson E, Towle V, Tao W, Acland GM, Aguirre GD, Zeiss CJ. CREB1/ATF1 Activation in Photoreceptor Degeneration and Protection. Investigative Ophthalmology & Visual Science 2009, 50: 5355-5363. PMID: 19643965, PMCID: PMC3172238, DOI: 10.1167/iovs.09-3741.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 1AgedAged, 80 and overAnimalsArrestinCell CountCiliary Neurotrophic FactorCyclic AMP Response Element-Binding ProteinDog DiseasesDogsFemaleGenotypeHumansImmunoblottingImmunoenzyme TechniquesMacular DegenerationMalePhosphorylationPhotoreceptor Cells, VertebrateRetinitis PigmentosaRhodopsinConceptsAge-related macular degenerationCiliary neurotrophic factorNormal canine retinaRcd1 dogsCanine retinaHuman retinaInnate protective responseNeuroprotective stimulusInner retinaNeurotrophic factorTranscription factor 1Macular degenerationRetinal protectionPhotoreceptor protectionP-CREB1Photoreceptor diseaseNormal dogsCanine modelPhotoreceptor degenerationRetinal degenerationProtective responseStrong immunolabelingCone photoreceptorsPhotoreceptor nucleiRetina
2000
A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I
Scharfe C, Hauschild M, Klopstock T, Janssen AJ, Heidemann PH, Meitinger T, Jaksch M. A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I. Journal Of Medical Genetics 2000, 37: 669. PMID: 10978358, PMCID: PMC1734685, DOI: 10.1136/jmg.37.9.669.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAnemia, MegaloblasticBase SequenceCarrier ProteinsConsanguinityDNADNA Mutational AnalysisElectron Transport Complex IFamily HealthFemaleHumansMaleMembrane Transport ProteinsMitochondria, MuscleMuscle, SkeletalMutationNADH, NADPH OxidoreductasesPedigreePoint MutationPyruvate Dehydrogenase ComplexPyruvate Dehydrogenase Complex Deficiency DiseaseThiamineConceptsComplex I activityEarly-onset autosomal recessive disorderHigh-dose thiamine supplementationBrain MRI lesionsThiamine-responsive megaloblastic anemiaAutosomal recessive disorderI activityMRI lesionsClinical featuresMegaloblastic anemiaSkin biopsiesThiamine supplementationThiamine deficiencyTypical triadSLC19A2 geneRetinal degenerationHigh dosesConsanguineous parentsShort statureMitochondrial energy productionMitochondrial abnormalitiesSevere deficiencyRecessive disorderRespiratory chain complex IChain complex I
1999
Implication of Tubby Proteins as Transcription Factors by Structure-Based Functional Analysis
Boggon T, Shan W, Santagata S, Myers S, Shapiro L. Implication of Tubby Proteins as Transcription Factors by Structure-Based Functional Analysis. Science 1999, 286: 2119-2125. PMID: 10591637, DOI: 10.1126/science.286.5447.2119.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAlternative SplicingAmino Acid SequenceAnimalsCell LineCell NucleusCrystallography, X-RayDNAEye ProteinsHumansIntercellular Signaling Peptides and ProteinsIntracellular Signaling Peptides and ProteinsModels, MolecularMolecular Sequence DataProtein ConformationProtein Structure, SecondaryProtein Structure, TertiaryProteinsRecombinant ProteinsSequence AlignmentTranscription FactorsTranscriptional ActivationConceptsTubby-like proteinsTubby proteinTranscription factorsBipartite transcription factorDisease phenotypeMulticellular organismsProtein familyBiochemical functionsBiological functionsFunctional analysisStructural cluesCore domainUnique familyProteinGenetic mutationsTubbyPhenotypeRetinal degenerationFamilyMammalsOrganismsVital roleCrystal structureMutationsBroad range
1996
Molecular Cloning and Domain Structure of Human Myosin-VIIa, the Gene Product Defective in Usher Syndrome 1B
Chen Z, Hasson T, Kelley P, Schwender B, Schwartz M, Ramakrishnan M, Kimberling W, Mooseker M, Corey D. Molecular Cloning and Domain Structure of Human Myosin-VIIa, the Gene Product Defective in Usher Syndrome 1B. Genomics 1996, 36: 440-448. PMID: 8884267, DOI: 10.1006/geno.1996.0489.Peer-Reviewed Original ResearchConceptsUsher syndrome 1BIntestinal epithelium cell lineProgressive retinal degenerationEpithelium cell lineVestibular functionMyosin VIIaPigment epitheliumRetinal degenerationInner earReceptor cellsRT-PCRBand 4.1 familyRestricted expressionShort formCell linesMembrane-associated portionHuman myosin VIIaMolecular cloningLong transcriptsTestisShort transcriptsUnconventional myosinLong repeatsHigh abundanceAmino acids
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