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Sci Rep. 2017 Apr 10;7(1):766. doi: 10.1038/s41598-017-00774-9.

Photoreceptor Outer Segment-like Structures in Long-Term 3D Retinas from Human Pluripotent Stem Cells.

Author information

1
Wilmer Eye Institute, The Johns Hopkins Wilmer Eye Institute 600 N. Wolfe Street, Baltimore, MD, 21287, USA.
2
Shiley Eye Institute, University of California San Diego, La Jolla, California, USA.
3
Is PhenoCell, Evry, France.
4
Retinal Neurophysiology Section, National Eye Institute, Bethesda, MD, USA.
5
Moran Eye Center, University of Utah, Salt Lake City, Utah, USA.
6
Wilmer Eye Institute, The Johns Hopkins Wilmer Eye Institute 600 N. Wolfe Street, Baltimore, MD, 21287, USA. dzack@jhmi.edu.
7
Department of Molecular Biology and Genetics, Neuroscience, and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. dzack@jhmi.edu.

Abstract

The retinal degenerative diseases, which together constitute a leading cause of hereditary blindness worldwide, are largely untreatable. Development of reliable methods to culture complex retinal tissues from human pluripotent stem cells (hPSCs) could offer a means to study human retinal development, provide a platform to investigate the mechanisms of retinal degeneration and screen for neuroprotective compounds, and provide the basis for cell-based therapeutic strategies. In this study, we describe an in vitro method by which hPSCs can be differentiated into 3D retinas with at least some important features reminiscent of a mature retina, including exuberant outgrowth of outer segment-like structures and synaptic ribbons, photoreceptor neurotransmitter expression, and membrane conductances and synaptic vesicle release properties consistent with possible photoreceptor synaptic function. The advanced outer segment-like structures reported here support the notion that 3D retina cups could serve as a model for studying mature photoreceptor development and allow for more robust modeling of retinal degenerative disease in vitro.

PMID:
28396597
PMCID:
PMC5429674
DOI:
10.1038/s41598-017-00774-9
[Indexed for MEDLINE]
Free PMC Article

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