March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Transplantation of Human Embryonic Stem Cell-Derived Retinal Cells into the Subretinal Space of a Non-Human Primate
Author Affiliations & Notes
  • Jennifer R. Chao
    Ophthalmology,
    University of Washington, Seattle, Washington
  • Deepak A. Lamba
    Buck Institute for Research on Aging, Novato, California
  • Todd Klesert
    University of Washington, Seattle, Washington
  • Kristin Sternhagen
    Ophthalmology,
    University of Washington, Seattle, Washington
  • Russell Taylor
    Ophthalmology,
    University of Washington, Seattle, Washington
  • Aya Yanagida
    Ophthalmology,
    University of Washington, Seattle, Washington
  • Maureen Neitz
    Ophthalmology,
    University of Washington, Seattle, Washington
  • Jay Neitz
    Ophthalmology, Univ of Washington, Medical School, Seattle, Washington
  • Ruikang K. Wang
    Bioengineering,
    University of Washington, Seattle, Washington
  • Thomas A. Reh
    Dept of Biological Structure,
    University of Washington, Seattle, Washington
  • Footnotes
    Commercial Relationships  Jennifer R. Chao, iScience Interventional (F); Deepak A. Lamba, None; Todd Klesert, None; Kristin Sternhagen, None; Russell Taylor, None; Aya Yanagida, None; Maureen Neitz, None; Jay Neitz, None; Ruikang K. Wang, None; Thomas A. Reh, None
  • Footnotes
    Support  Foundation Fighting Blindness TA-CBT-0608-0464-UWA-WG
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5839. doi:https://doi.org/
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      Jennifer R. Chao, Deepak A. Lamba, Todd Klesert, Kristin Sternhagen, Russell Taylor, Aya Yanagida, Maureen Neitz, Jay Neitz, Ruikang K. Wang, Thomas A. Reh; Transplantation of Human Embryonic Stem Cell-Derived Retinal Cells into the Subretinal Space of a Non-Human Primate. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5839. doi: https://doi.org/.

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

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Abstract

Purpose: : Previous studies have demonstrated the ability of retinal cells derived from human embryonic stem cells (hESCs) to survive, integrate into the host retina circuit, and mediate light responses in previously blind mice when injected into the subretinal space. Our aim is to determine whether retinal cells derived from hESCs can survive and integrate into the host retina following transplantation into the subretinal space of a non-human primate, Saimiri sciureus.

Methods: : hESCs were differentiated towards retinal neuronal fates using our previously published technique and cultured for 70-80 days. Differentiated cells were further treated with 20µM DAPT for 5 days prior to the subretinal injection. Differentiated cells were transduced with a lentivirus expressing GFP under the control of the EF-1α promoter. One million cells in a volume of 100µl (10,000 cells/µl) were injected into the subretinal space in one eye of a squirrel monkey, using an ab externo technique.

Results: : RetCam and OCT imaging revealed the presence and survival of transplanted cells three months post-injection. Injected cells were consolidated in the posterior pole temporal to the fovea in an area with a shallow retinal detachment. Fluorescent axonal projections were noted to emanate from the central consolidation of cells, with some projecting to the optic nerve.

Conclusions: : Human ES cell-derived retinal neurons injected into the subretinal space of a squirrel monkey (Saimiri sciureus) appear to survive up to three months post-injection without immunosuppression. In addition, the injected cells were noted to extend axonal projections in the host retina. Further studies, will be required to determine the extent of integration and potential function of the transplanted cells.

Keywords: retina • differentiation • retinal culture 
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