Details

Autor(en) / Beteiligte

• Quinn, Peter M.
• Buck, Thilo M.
• Mulder, Aat A.
• Ohonin, Charlotte
• Alves, C. Henrique
• Vos, Rogier M.
• Bialecka, Monika
• van Herwaarden, Tessa
• van Dijk, Elon H.C.
• Talib, Mays
• Freund, Christian
• Mikkers, Harald M.M.
• Hoeben, Rob C.
• Goumans, Marie-José
• Boon, Camiel J.F.
• Koster, Abraham J.
• Chuva de Sousa Lopes, Susana M.
• Jost, Carolina R.
• Wijnholds, Jan

Titel

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

Ist Teil von

• Stem cell reports, 2019-05, Vol.12 (5), p.906-919

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •iPSC-derived retinas recapitulate the fetal human Crumbs complex•CRB2 is expressed earlier than CRB1 in fetal or iPSC-derived retina at the SAR•CRB1-RP patient iPSC-derived retinas show disruptions at the OLM•AAV5 infects photoreceptors and Müller glial cells in adult and iPSC-derived retina Wijnholds and colleagues show that the key Crumbs complex members, CRB1 and CRB2, are recapitulated between human fetal retina and iPSC-derived retinal organoids. CRB2 is expressed earlier than CRB1 in fetal and iPSC-derived human retina. CRB1-RP patient iPSC-derived retinas show a morphological phenotype. In addition, they show that AAV5 infects photoreceptors and Müller glial cells in adult and iPSC-derived human retina.