Modeling PRPF31 retinitis pigmentosa using retinal pigment epithelium and organoids combined with gene augmentation rescue
| Autor: | Amélie Rodrigues, Amélie Slembrouck-Brec, Céline Nanteau, Angélique Terray, Yelyzaveta Tymoshenko, Yvrick Zagar, Sacha Reichman, Zhouhuan Xi, José-Alain Sahel, Stéphane Fouquet, Gael Orieux, Emeline F. Nandrot, Leah C. Byrne, Isabelle Audo, Jérôme E. Roger, Olivier Goureau |
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| Přispěvatelé: | Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Centre d'investigation clinique Quinze-Vingts [CHNO] (CIC1423 - CIC QUINZE-VINGTS), Institut Hospitalo-Universitaire FOReSIGHT, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-Sorbonne Université (SU), Goureau, Olivier |
| Rok vydání: | 2021 |
| Předmět: |
[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs
Biomedical Engineering [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Medicine (miscellaneous) [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Cell Biology [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs Developmental Biology |
| Zdroj: | NPJ Regenerative medicine NPJ Regenerative medicine, 2022, 7, pp.39. ⟨10.1038/s41536-022-00235-6⟩ |
| ISSN: | 2057-3995 |
| Popis: | Mutations in the ubiquitously expressedpre-mRNA processing factor(PRPF)31gene, one of the most common causes of dominant form of Retinitis Pigmentosa (RP), lead to a retina-specific phenotype. It is uncertain which retinal cell types are affected and animal models do not clearly present the RP phenotype observed inPRPF31patients. Retinal organoids and retinal pigment epithelial (RPE) cells derived from human-induced pluripotent stem cells (iPSCs) provide potential opportunities for studying humanPRPF31-related RP. We demonstrate here that RPE cells carryingPRPF31mutations present important morphological and functional changes and thatPRPF31-mutated retinal organoids recapitulate the human RP phenotype, with a rod photoreceptor cell death followed by a loss of cones. The low level ofPRPF31expression may explain the defective phenotypes ofPRPF31-mutated RPE and photoreceptor cells, which were not observed in cells derived from asymptomatic patients or after correction of the pathogenic mutation by CRISPR/Cas9. Transcriptome profiles revealed differentially expressed and mis-spliced genes belonging to pathways in line with the observed defective phenotypes. The rescue of RPE and photoreceptor defective phenotypes byPRPF31gene augmentation provide the proof of concept for future therapeutic strategies. |
| Databáze: | OpenAIRE |
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