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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Cell Culture Techniques
  • Cell Differentiation*
  • Cells, Cultured
  • Cytoplasmic Vesicles / metabolism
  • Cytoplasmic Vesicles / ultrastructure
  • Gene Expression
  • Humans
  • Hypoxia
  • Pluripotent Stem Cells / cytology*
  • Retina / cytology*
  • Retina / metabolism*
  • Retinal Cone Photoreceptor Cells / cytology
  • Retinal Cone Photoreceptor Cells / metabolism
  • Retinal Photoreceptor Cell Outer Segment / metabolism*
  • Retinal Rod Photoreceptor Cells / cytology
  • Retinal Rod Photoreceptor Cells / metabolism
  • Time Factors

Substances

  • Biomarkers