Lane, A;
Jovanovic, K;
Shortall, C;
Ottaviani, D;
Panes, AB;
Schwarz, N;
Guarascio, R;
... Cheetham, ME; + view all
(2020)
Modeling and Rescue of RP2 Retinitis Pigmentosa Using iPSC-Derived Retinal Organoids.
Stem Cell Reports
10.1016/j.stemcr.2020.05.007.
(In press).
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Abstract
RP2 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.
| Type: | Article |
|---|---|
| Title: | Modeling and Rescue of RP2 Retinitis Pigmentosa Using iPSC-Derived Retinal Organoids |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.stemcr.2020.05.007 |
| Publisher version: | https://doi.org/10.1016/j.stemcr.2020.05.007 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | AAV, CRISPR gene editing, cell death, disease modeling, gene therapy, genetic, inherited disease, retinal degeneration, retinal organoid, stem cell |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10101662 |
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