Modeling PRPF31 retinitis pigmentosa using retinal pigment epithelium and organoids combined with gene augmentation rescue - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue NPJ Regenerative medicine Année : 2022

Modeling PRPF31 retinitis pigmentosa using retinal pigment epithelium and organoids combined with gene augmentation rescue

Sacha Reichman
Emeline F Nandrot
Olivier Goureau

Résumé

Mutations in the ubiquitously expressed pre-mRNA processing factor (PRPF) 31 gene, 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 in PRPF31 patients. Retinal organoids and retinal pigment epithelial (RPE) cells derived from human-induced pluripotent stem cells (iPSCs) provide potential opportunities for studying human PRPF31-related RP. We demonstrate here that RPE cells carrying PRPF31 mutations present important morphological and functional changes and that PRPF31-mutated retinal organoids recapitulate the human RP phenotype, with a rod photoreceptor cell death followed by a loss of cones. The low level of PRPF31 expression may explain the defective phenotypes of PRPF31-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 by PRPF31 gene augmentation provide the proof of concept for future therapeutic strategies.
Fichier principal
Vignette du fichier
Rodrigues et al. (npj Reg Med 2022).pdf (12.76 Mo) Télécharger le fichier
Rodrigues - iPSC PRPF31 organoids RPE (npj Reg Med 2022) Supp.pdf (9.73 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03774125 , version 1 (09-09-2022)

Identifiants

Citer

Amélie Rodrigues, Amélie Slembrouck-Brec, Céline Nanteau, Angélique Terray, Yelyzaveta Tymoshenko, et al.. Modeling PRPF31 retinitis pigmentosa using retinal pigment epithelium and organoids combined with gene augmentation rescue. NPJ Regenerative medicine, 2022, 7, pp.39. ⟨10.1038/s41536-022-00235-6⟩. ⟨hal-03774125⟩
69 Consultations
45 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More