title: Photoreceptor Outer Segment-like Structures in Long-Term 3D Retinas from Human Pluripotent Stem Cells.
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.
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins Wilmer Eye Institute 600 N. Wolfe Street, Baltimore, MD, 21287, USA.|Shiley Eye Institute, University of California San Diego, La Jolla, California, USA.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Wahlin
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins Wilmer Eye Institute 600 N. Wolfe Street, Baltimore, MD, 21287, USA.|Is PhenoCell, Evry, France.
authors.forename: Julien A
authors.initials: JA
authors.lastname: Maruotti
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins Wilmer Eye Institute 600 N. Wolfe Street, Baltimore, MD, 21287, USA.
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Sripathi
authors.affiliation: Retinal Neurophysiology Section, National Eye Institute, Bethesda, MD, USA.
authors.forename: John
authors.initials: J
authors.lastname: Ball
authors.affiliation: Retinal Neurophysiology Section, National Eye Institute, Bethesda, MD, USA.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Angueyra
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins Wilmer Eye Institute 600 N. Wolfe Street, Baltimore, MD, 21287, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Kim
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins Wilmer Eye Institute 600 N. Wolfe Street, Baltimore, MD, 21287, USA.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Grebe
authors.affiliation: Retinal Neurophysiology Section, National Eye Institute, Bethesda, MD, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Moran Eye Center, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Jones
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins Wilmer Eye Institute 600 N. Wolfe Street, Baltimore, MD, 21287, USA. dzack@jhmi.edu.|Department of Molecular Biology and Genetics, Neuroscience, and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. dzack@jhmi.edu.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Zack
mesh_terms: D015415:Biomarkers; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression; D006801:Humans; D000860:Hypoxia; D039904:Pluripotent Stem Cells / Q000166:cytology*; D012160:Retina / Q000166:cytology* / Q000378:metabolism*; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D055214:Retinal Photoreceptor Cell Outer Segment / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers