Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5.
Stem Cell Reports
; 12(5): 906-919, 2019 05 14.
Article
em En
| MEDLINE
| ID: mdl-30956116
ABSTRACT
Human retinal organoids from induced pluripotent stem cells (hiPSCs) can be used to confirm the localization of proteins in retinal cell types and to test transduction and expression patterns of gene therapy vectors. Here, we compared the onset of CRB protein expression in human fetal retina with human iPSC-derived retinal organoids. We show that CRB2 protein precedes the expression of CRB1 in the developing human retina. Our data suggest the presence of CRB1 and CRB2 in human photoreceptors and Müller glial cells. Thus the fetal CRB complex formation is replicated in hiPSC-derived retina. CRB1 patient iPSC retinal organoids showed disruptions at the outer limiting membrane as found in Crb1 mutant mice. Furthermore, AAV serotype 5 (AAV5) is potent in infecting human Müller glial cells and photoreceptors in hiPSC-derived retinas and retinal explants. Our data suggest that human photoreceptors can be efficiently transduced by AAVs in the presence of photoreceptor segments.
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MEDLINE
Assunto principal:
Retina
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Proteínas de Transporte
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Organoides
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Células Fotorreceptoras de Vertebrados
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Proteínas do Olho
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Células-Tronco Pluripotentes Induzidas
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Células Ependimogliais
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Proteínas de Membrana
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Proteínas do Tecido Nervoso
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article