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dc.contributor.authorLane, Ameliaen
dc.contributor.authorJovanovic, Katarinaen
dc.contributor.authorShortall, Ciaraen
dc.contributor.authorOttaviani, Danieleen
dc.contributor.authorBrugulat-Panes, Annaen
dc.contributor.authorSchwarz, Neleen
dc.contributor.authorGuarascio, Rosellinaen
dc.contributor.authorHayes, Matthew Jen
dc.contributor.authorPalfi, Arpaden
dc.contributor.authorChadderton, Naomien
dc.contributor.authorFarrar, G Janeen
dc.contributor.authorHardcastle, Alison Jen
dc.contributor.authorCheetham, Michael Een
dc.date.accessioned2020-07-07T14:43:58Z
dc.date.available2020-07-07T14:43:58Z
dc.identifier.issn2213-6711
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/307707
dc.description.abstractRP2 mutations cause a severe form of X-linked retinitis pigmentosa (XLRP). The mechanism of RP2-associated retinal degeneration in humans is unclear, and animal models of RP2 XLRP do not recapitulate this severe phenotype. Here, we developed gene-edited isogenic RP2 knockout (RP2 KO) induced pluripotent stem cells (iPSCs) and RP2 patient-derived iPSC to produce 3D retinal organoids as a human retinal disease model. Strikingly, the RP2 KO and RP2 patient-derived organoids showed a peak in rod photoreceptor cell death at day 150 (D150) with subsequent thinning of the organoid outer nuclear layer (ONL) by D180 of culture. Adeno-associated virus-mediated gene augmentation with human RP2 rescued the degeneration phenotype of the RP2 KO organoids, to prevent ONL thinning and restore rhodopsin expression. Notably, these data show that 3D retinal organoids can be used to model photoreceptor degeneration and test potential therapies to prevent photoreceptor cell death
dc.language.isoenen
dc.publisherElsevier
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleModeling and Rescue of RP2 Retinitis Pigmentosa Using iPSC-Derived Retinal Organoidsen
dc.typeArticle
prism.publicationNameStem Cell Reportsen
dc.identifier.doi10.17863/CAM.54801
dcterms.dateAccepted2020-05-13en
rioxxterms.versionofrecord10.1016/j.stemcr.2020.05.007en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-05-13en
dc.identifier.eissn1552-5783
rioxxterms.typeJournal Article/Reviewen
cam.issuedOnline2020-06-11en


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International