Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5

TY - JOUR

T1 - Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5

AU - Quinn, Peter M

AU - Buck, Thilo M

AU - Mulder, Aat A

AU - Ohonin, Charlotte

AU - Alves, C Henrique

AU - Vos, Rogier M

AU - Bialecka, Monika

AU - van Herwaarden, Tessa

AU - van Dijk, Elon H C

AU - Talib, Mays

AU - Freund, Christian

AU - Mikkers, Harald M M

AU - Hoeben, Rob C

AU - Goumans, Marie-José

AU - Boon, Camiel J F

AU - Koster, Abraham J

AU - Chuva de Sousa Lopes, Susana M

AU - Jost, Carolina R

AU - Wijnholds, Jan

N1 - Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1016/j.stemcr.2019.03.002

DO - 10.1016/j.stemcr.2019.03.002

M3 - Article

C2 - 30956116

SN - 2213-6711

VL - 12

SP - 906

EP - 919

JO - Stem Cell Reports

JF - Stem Cell Reports

ER -