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
2010
REVIEW PAPER: Animals as Models of Age-Related Macular Degeneration
Zeiss CJ. REVIEW PAPER: Animals as Models of Age-Related Macular Degeneration. Veterinary Pathology 2010, 47: 396-413. PMID: 20382825, DOI: 10.1177/0300985809359598.Peer-Reviewed Original ResearchConceptsAge-related macular degenerationMacular degenerationRelevant mouse modelNonhuman primate modelCause of blindnessRetinal pigment epitheliumMajority of casesEtiologic complexityAMD pathologyChoroidal neovascularizationEtiologic factorsModel of agePrimate modelRodent retinaPathogenetic mechanismsMouse modelGenetic predispositionSalient anatomyPigment epitheliumAnimal modelsDegenerative conditionsComplement activationLipid metabolismBruch's membraneGene function
2006
Safety in Nonhuman Primates of Ocular AAV2-RPE65, a Candidate Treatment for Blindness in Leber Congenital Amaurosis
Jacobson SG, Boye SL, Aleman TS, Conlon TJ, Zeiss CJ, Roman AJ, Cideciyan AV, Schwartz SB, Komaromy AM, Doobrajh M, Cheung AY, Sumaroka A, Pearce-Kelling SE, Aguirre GD, Kaushal S, Maguire AM, Flotte TR, Hauswirth WW. Safety in Nonhuman Primates of Ocular AAV2-RPE65, a Candidate Treatment for Blindness in Leber Congenital Amaurosis. Human Gene Therapy 2006, 17: 845-858. PMID: 16942444, DOI: 10.1089/hum.2006.17.845.Peer-Reviewed Original ResearchConceptsLeber congenital amaurosisOptic nerveGood Laboratory Practice safety studiesCongenital amaurosisObserved adverse effect levelSafety studiesRPE65-mutant dogsSingle intraocular injectionVector-injected eyesHeterogeneous disease groupNormal cynomolgus monkeysAdverse effect levelFuture human trialsGene transfer trialsDose-dependent mannerHigh vector dosesPresurgical recordingsRetinal histopathologyInjected eyeControl eyesIntraocular injectionRetinal injuryCentral retinaThickness abnormalitiesClinical examinationSafety of Recombinant Adeno-Associated Virus Type 2–RPE65 Vector Delivered by Ocular Subretinal Injection
Jacobson SG, Acland GM, Aguirre GD, Aleman TS, Schwartz SB, Cideciyan AV, Zeiss CJ, Komaromy AM, Kaushal S, Roman AJ, Windsor EA, Sumaroka A, Pearce-Kelling SE, Conlon TJ, Chiodo VA, Boye SL, Flotte TR, Maguire AM, Bennett J, Hauswirth WW. Safety of Recombinant Adeno-Associated Virus Type 2–RPE65 Vector Delivered by Ocular Subretinal Injection. Molecular Therapy 2006, 13: 1074-1084. PMID: 16644289, DOI: 10.1016/j.ymthe.2006.03.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedBlindnessCarrier ProteinsCis-trans-IsomerasesDependovirusDogsDose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsEye ProteinsFemaleGenetic TherapyGenetic VectorsInjections, IntralesionalMaleOptic Atrophy, Hereditary, LeberRatsRats, Sprague-DawleyRecombinant ProteinsRetinaTissue DistributionConceptsRPE65-mutant dogsLeber congenital amaurosisMonths postinjectionHuman trialsBiodistribution studiesVector dosesHigh vector dosesOcular examinationRetinal histopathologyInjected eyeOptic nerveDose-response resultsModerate inflammationNormal ratsTraumatic lesionsDose efficacyVisual centersSubretinal injectionRPE65 geneSystemic toxicityVirus typeCongenital amaurosisOcular deliveryPostinjectionDoses
2005
CNTF induces dose-dependent alterations in retinal morphology in normal and rcd-1 canine retina
Zeiss CJ, Allore HG, Towle V, Tao W. CNTF induces dose-dependent alterations in retinal morphology in normal and rcd-1 canine retina. Experimental Eye Research 2005, 82: 395-404. PMID: 16143329, DOI: 10.1016/j.exer.2005.07.014.Peer-Reviewed Original ResearchConceptsCiliary neurotrophic factorInner retinal thicknessRetinitis pigmentosaRetinal thicknessGanglion cellsEffects of CNTFInner nuclear layer thicknessNormal retinal electrophysiologyGanglion cell morphologyOuter nuclear layerWild-type retinasDose-dependent mannerDose-dependent alterationsContralateral eyeControl dogsNeurotrophic factorExpression of rhodopsinRetinal electrophysiologyNuclear layerProtective effectRetinal morphologyEntire retinaAnimal modelsCone arrestinCanine model
2004
Caspase-3 in Postnatal Retinal Development and Degeneration
Zeiss CJ, Neal J, Johnson EA. Caspase-3 in Postnatal Retinal Development and Degeneration. Investigative Ophthalmology & Visual Science 2004, 45: 964-970. PMID: 14985318, DOI: 10.1167/iovs.03-0439.Peer-Reviewed Original ResearchConceptsTerminal dUTP transferase nick end labelingPostnatal retinal developmentCaspase-3Photoreceptor degenerationRod deathMutant miceRetinal developmentInner nuclear layerDouble mutant miceNick end labelingLight microscopic levelRod photoreceptor developmentCell nuclear antigenNeonatal deathRetinal morphometryDysplastic lesionsRetinal dysplasiaNuclear layerPhotoreceptor protectionImmunohistochemical stainingRodent modelsFactor VIICaspase-3 activationNuclear antigenEnd labeling