Modeling and Rescue of RP2 Retinitis Pigmentosa Using iPSC-Derived Retinal Organoids

被引：119

作者：

Lane, Amelia ^{[1
]}

Jovanovic, Katarina ^{[1
]}

Shortall, Ciara ^{[2
]}

Ottaviani, Daniele ^{[1
]}

Panes, Anna Brugulat ^{[1
]}

Schwarz, Nele ^{[1
]}

Guarascio, Rosellina ^{[1
]}

Hayes, Matthew J. ^{[1
]}

Palfi, Arpad ^{[2
]}

Chadderton, Naomi ^{[2
]}

Farrar, G. Jane ^{[2
]}

Hardcastle, Alison J. ^{[1
]}

Cheetham, Michael E. ^{[1
]}

机构：

[1] UCL Inst Ophthalmol, London, England

[2] Trinity Coll Dublin, Smurfit Inst Genet, Dublin 2, Ireland

来源：

STEM CELL REPORTS | 2020年 / 15卷 / 01期

基金：

英国惠康基金; 英国国家替代、减少和改良动物研究中心; 爱尔兰科学基金会;

关键词：

PLURIPOTENT STEM-CELLS; PROTEIN RP2; GENE; VECTORS; TISSUE; TRANSPLANTATION; REPLACEMENT; TRAFFICKING; EXPRESSION; TRANSPORT;

D O I：

10.1016/j.stemcr.2020.05.007

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 po-tential to cell death.

引用

页码：67 / 79

页数：13

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