March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Retinal Laminae Formation and Synapse Development in Optic Vesicle-like Structures Isolated from Human Blood-derived iPS Cells
Author Affiliations & Notes
  • Joe Phillips
    Waisman Center,
    University of Wisconsin, Madison, Wisconsin
  • Kyle A. Wallace
    Waisman Center,
    University of Wisconsin, Madison, Wisconsin
  • Sarah Dickerson
    Cellular Dynamics International, Madison, Wisconsin
  • Michael Miller
    Cellular Dynamics International, Madison, Wisconsin
  • Amelia D. Gerner
    Waisman Center,
    University of Wisconsin, Madison, Wisconsin
  • Jessica M. Martin
    Waisman Center,
    University of Wisconsin, Madison, Wisconsin
  • Lynda S. Wright
    Waisman Center,
    University of Wisconsin, Madison, Wisconsin
  • Elizabeth E. Capowski
    Waisman Center,
    University of Wisconsin, Madison, Wisconsin
  • Enio T. Perez
    Waisman Center,
    University of Wisconsin, Madison, Wisconsin
  • David M. Gamm
    Department of Ophthalmology, Visual Sciences, and Eye Research Institute,
    University of Wisconsin, Madison, Wisconsin
  • Footnotes
    Commercial Relationships  Joe Phillips, None; Kyle A. Wallace, None; Sarah Dickerson, CDI (E); Michael Miller, CDI (E); Amelia D. Gerner, None; Jessica M. Martin, None; Lynda S. Wright, None; Elizabeth E. Capowski, None; Enio T. Perez, None; David M. Gamm, None
  • Footnotes
    Support  FFB Wynn-Gund Translational Research Acceleration Award; NIH R01EY21218; P30HD03352; Retina Research Foundation; UW-ICTR NIH 1UL1RR025011; UW Eye Research Institute; E. Matilda Ziegler Foundation
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 2692. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Joe Phillips, Kyle A. Wallace, Sarah Dickerson, Michael Miller, Amelia D. Gerner, Jessica M. Martin, Lynda S. Wright, Elizabeth E. Capowski, Enio T. Perez, David M. Gamm; Retinal Laminae Formation and Synapse Development in Optic Vesicle-like Structures Isolated from Human Blood-derived iPS Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2692.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: : We sought to determine if human induced pluripotent stem cells (iPSCs) derived from peripheral blood could generate optic vesicle-like structures (OVs) with the capacity to stratify and express markers of intercellular communication.

Methods: : Activated T-lymphocytes from a routine peripheral blood sample were reprogrammed by retroviral transduction to iPSCs. The T-lymphocyte-derived iPSCs (TiPSCs) were characterized for pluripotency and differentiated to OVs containing a highly enriched population of neuroretinal progenitor cells (NRPCs). TiPSC-OVs were then manually isolated, pooled, and cultured en masse to more mature stages of retinogenesis. Throughout the stepwise differentiation process, changes in anterior neural, retinal, and synaptic marker expression were monitored by PCR, immunocytochemistry, and/or flow cytometry.

Results: : TiPSCs generated OVs in abundance, which contained a near homogenous population of proliferating NRPCs. These NRPCs differentiated into multiple neuroretinal cell types, similar to OV cultures from human embryonic stem cells and fibroblast-derived iPSCs. In addition, portions of some TiPSC-OVs maintained a distinctive neuroepithelial appearance and spontaneously formed primitive laminae, reminiscent of the developing retina. Retinal progeny from TiPSC-OV cultures upregulated numerous genes and expressed proteins critical for synaptogenesis and gap junction formation, concomitant with the emergence of glia and the expression of thrombospondins in culture.

Conclusions: : We demonstrate for the first time that human blood-derived iPSCs can generate retinal cell types, providing a highly convenient donor cell source for iPSC-based retinal studies. We also show that cultured human iPSC-OVs have the capacity to self-assemble into rudimentary neuroretinal structures and express markers indicative of chemical and electrical synapses.

Keywords: retinal development • retinal culture • synapse 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×