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
Safety and Efficacy of AAV5 Vectors Expressing Human or Canine CNGB3 in CNGB3-Mutant Dogs
Ye GJ, Komáromy AM, Zeiss C, Calcedo R, Harman CD, Koehl KL, Stewart GA, Iwabe S, Chiodo VA, Hauswirth WW, Aguirre GD, Chulay JD. Safety and Efficacy of AAV5 Vectors Expressing Human or Canine CNGB3 in CNGB3-Mutant Dogs. Human Gene Therapy 2017, 28: 197-207. PMID: 29020838, PMCID: PMC5733651, DOI: 10.1089/humc.2017.125.Peer-Reviewed Original ResearchConceptsHuman CNGB3Immune responseHigh dosesT cell immune responsesHigh-dose groupLow-dose groupInherited retinal disorderImmune-mediated toxicitiesHigher vector doseCone photoreceptor functionDifferent dose levelsFocal chorioretinitisRetinal toxicityVisual acuityInflammatory responseAAV vectorsRetinal disordersSubretinal injectionCone functionDose levelsCone photoreceptorsPhotoreceptor functionCNGB3AAV5 vectorVector dose
2011
A slowly progressive retinopathy in the Shetland Sheepdog
Karlstam L, Hertil E, Zeiss C, Ropstad EO, Bjerkås E, Dubielzig RR, Ekesten B. A slowly progressive retinopathy in the Shetland Sheepdog. Veterinary Ophthalmology 2011, 14: 227-238. PMID: 21733063, DOI: 10.1111/j.1463-5224.2010.00866.x.Peer-Reviewed Original ResearchConceptsB-wave amplitudeRod-cone degenerationOphthalmoscopic signsProgressive retinopathyProgressive retinal atrophyShetland SheepdogsTapetal fundusOphthalmoscopic changesRetinal atrophyProgressive rod-cone degenerationSlit-lamp biomicroscopyOuter nuclear layerOphthalmoscopic findingsOphthalmic examinationNuclear layerNormal dogsCone outer segmentsGreyish discolorationRepeated examinationsAbnormal appearanceVisual impairmentRetinopathyDogsMicroscopic examinationForty adults
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
2008
Reversal of Blindness in Animal Models of Leber Congenital Amaurosis Using Optimized AAV2-mediated Gene Transfer
Bennicelli J, Wright JF, Komaromy A, Jacobs JB, Hauck B, Zelenaia O, Mingozzi F, Hui D, Chung D, Rex TS, Wei Z, Qu G, Zhou S, Zeiss C, Arruda VR, Acland GM, Dell'Osso LF, High KA, Maguire AM, Bennett J. Reversal of Blindness in Animal Models of Leber Congenital Amaurosis Using Optimized AAV2-mediated Gene Transfer. Molecular Therapy 2008, 16: 458-465. PMID: 18209734, PMCID: PMC2842085, DOI: 10.1038/sj.mt.6300389.Peer-Reviewed Original ResearchConceptsLeber congenital amaurosisAnimal modelsCongenital amaurosisReversal of blindnessRetinal pigment epithelium cellsWeeks of injectionPigment epithelium cellsRPE65 formDose of vectorAppropriate target cellsVisual acuityVisual deficitsHistopathologic analysisAdeno-associated virusERG responsesRPE65 mutationsSubretinal deliveryEpithelium cellsMutant miceMinimal toxicityProtein expressionTarget cellsPupillary responseElectroretinogramAmaurosis
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
A morphologic study of intravitreal membranes associated with intraocular hemorrhage in the dog
Zeiss CJ, Dubielzig RR. A morphologic study of intravitreal membranes associated with intraocular hemorrhage in the dog. Veterinary Ophthalmology 2004, 7: 239-243. PMID: 15200620, DOI: 10.1111/j.1463-5224.2004.04033.x.Peer-Reviewed Original ResearchConceptsGlial fibrillary acidic proteinSmooth muscle actinRetinal neovascularizationIntravitreal hemorrhageMuscle actinFactor VIII-related antigenIntravitreal membranesAdditional common findingsOptic disc cuppingVIII-related antigenFibrillary acidic proteinDisc cuppingIntraocular hemorrhageFibrovascular membranesCommon findingEpiretinal membraneGlial originHemorrhageImmunohistochemical proceduresSpringer spanielAcidic proteinLabrador RetrieversStandard histologyMorphologic studiesDogs