| Autor: |
Nanda Boon, Xuefei Lu, Charlotte A. Andriessen, Ioannis Moustakas, Thilo M. Buck, Christian Freund, Christiaan H. Arendzen, Stefan Böhringer, Camiel J.F. Boon, Hailiang Mei, Jan Wijnholds |
| Přispěvatelé: |
Netherlands Institute for Neuroscience (NIN) |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Stem Cell Reports, 18, 1123-1137. Cell Press |
| ISSN: |
2213-6711 |
| Popis: |
Retinitis pigmentosa and Leber congenital amaurosis are inherited retinal dystrophies that can be caused by mutations in the Crumbs homolog 1 (CRB1) gene. CRB1 is required for organizing apical-basal polarity and adhesion between photoreceptors and Müller glial cells. CRB1 patient-derived induced pluripotent stem cells were differentiated into CRB1 retinal organoids that showed diminished expression of variant CRB1 protein observed by immunohistochemical analysis. Single-cell RNA sequencing revealed impact on, among others, the endosomal pathway and cell adhesion and migration in CRB1 patient-derived retinal organoids compared with isogenic controls. Adeno-associated viral (AAV) vector-mediated hCRB2 or hCRB1 gene augmentation in Müller glial and photoreceptor cells partially restored the histological phenotype and transcriptomic profile of CRB1 patient-derived retinal organoids. Altogether, we show proof-of-concept that AAV.hCRB1 or AAV.hCRB2 treatment improved the phenotype of CRB1 patient-derived retinal organoids, providing essential information for future gene therapy approaches for patients with mutations in the CRB1 gene. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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