Age-Dependent Disease Expression Determines Remodeling of the Retinal Mosaic in Carriers of RPGR Exon ORFn15 Mutations

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dc.contributor.authorBeltran, William
dc.contributor.authorAguirre, Gustavo D
dc.contributor.authorBeltran, William
dc.contributor.authorAguirre, Gustavo D
dc.contributor.authorAcland, Gregory M
dc.date2023-05-17T11:19:48.000
dc.date.accessioned2023-05-23T04:44:19Z
dc.date.available2023-05-23T04:44:19Z
dc.date.issued2009-08-01
dc.date.submitted2015-04-08T09:38:29-07:00
dc.description.abstractPURPOSE. To characterize the retinal histopathology in carriers of X-linked progressive retinal atrophy (XLPRA1 and XLPRA2), two canine models of X-linked retinitis pigmentosa caused, respectively, by a stop and a frameshift mutation in RPGRORF15. METHODS. Retinas of XLPRA2 and XLPRA1 carriers of different ages were processed for morphologic evaluation, TUNEL assay, and immunohistochemistry. Cell-specific markers were used to examine retinal remodeling events. RESULTS. A mosaic pattern composed of patches of diseased and normal retina was first detected in XLPRA2 carriers at 4.9 weeks of age. A peak of photoreceptor cell death led to focal rod loss; however, in these patches an increased density of cones was found to persist over time. Patches of disease gradually disappeared so that by 39 weeks of age the overall retinal morphology, albeit thinner, had improved lamination. In older XLPRA2 carriers (≥8.8 years), extended regions of severe degeneration occurred in the peripheral/mid-peripheral retina. In XLPRA1 carriers, opsin mislocalization and rare events of rod death were detected by TUNEL assay at 20 weeks of age; however, only patchy degeneration was seen by 1.4 years and was still apparent at 7.8 years. CONCLUSIONS. The time of onset and the progression of the disease differed between the two models. In the early-onset form (XLPRA2) the morphologic appearance of the retinal mosaic changed as a function of age, suggesting that structural plasticity persists in the early postnatal canine retina as mutant photoreceptors die. In the late-onset form (XLPRA1), patches of disease persisted until later ages.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/48862
dc.legacy.articleid1106
dc.legacy.fields10.1167/iovs.08-3364
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1106&context=vet_papers&unstamped=1
dc.source.beginpage3985
dc.source.endpage3995
dc.source.issue104
dc.source.issue8
dc.source.journalDepartmental Papers (Vet)
dc.source.journaltitleInvestigative Ophthalmology & Visual Science
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume50
dc.subject.otherretinal cell biology
dc.subject.otherEye Diseases
dc.subject.otherMedical Cell Biology
dc.subject.otherOphthalmology
dc.subject.otherOptometry
dc.subject.otherVeterinary Medicine
dc.titleAge-Dependent Disease Expression Determines Remodeling of the Retinal Mosaic in Carriers of RPGR Exon ORFn15 Mutations
dc.typeArticle
digcom.contributor.authorisAuthorOfPublication|email:wbeltran@vet.upenn.edu|institution:University of Pennsylvania|Beltran, William
digcom.contributor.authorAcland, Gregory M
digcom.contributor.authorisAuthorOfPublication|email:gda@vet.upenn.edu|institution:University of Pennsylvania|Aguirre, Gustavo D
digcom.identifiervet_papers/104
digcom.identifier.contextkey6958346
digcom.identifier.submissionpathvet_papers/104
digcom.typearticle
dspace.entity.typePublication
person.identifier.orcid0000-0002-5228-256X
person.identifier.orcid0000-0002-5228-256X
relation.isAuthorOfPublicationce628e7c-dff0-4210-9d35-d3494f5eee01
relation.isAuthorOfPublication1a18ef39-6294-4816-a00d-fe4b64c3295a
relation.isAuthorOfPublication.latestForDiscoveryce628e7c-dff0-4210-9d35-d3494f5eee01
upenn.schoolDepartmentCenterDepartmental Papers (Vet)
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