April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Human Embryonic Derived Neural Stem Cells Preserved Vision in Rodent Retinal Degeneration Model
Author Affiliations & Notes
  • Bin Lu
    Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • SiokLam Lim
    Ophthalmology and Human Genetics, UCSD, La Jolla, California
  • WenLin Li
    Chemistry, The Scripps Research Institute, La Jolla, California
  • Catherine W. Morgans
    Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • sergje girman
    Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • Justine Smith
    Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • Ray Lund
    Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • Sheng Ding
    Chemistry, The Scripps Research Institute, La Jolla, California
  • Kang Zhang
    Ophthalmology and Human Genetics, UCSD, La Jolla, California
  • Shaomei Wang
    Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • Footnotes
    Commercial Relationships  Bin Lu, None; SiokLam Lim, None; WenLin Li, None; Catherine W. Morgans, None; sergje girman, None; Justine Smith, None; Ray Lund, None; Sheng Ding, None; Kang Zhang, None; Shaomei Wang, None
  • Footnotes
    Support  FFB, Lincy Foundation, RBP, Burroughs Wellcome Fund, RO1EY14428, R01EY14448. R01EY18660. Transformative R01EY021374-01
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3176. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Bin Lu, SiokLam Lim, WenLin Li, Catherine W. Morgans, sergje girman, Justine Smith, Ray Lund, Sheng Ding, Kang Zhang, Shaomei Wang; Human Embryonic Derived Neural Stem Cells Preserved Vision in Rodent Retinal Degeneration Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3176.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : Cell-based therapies have shown promise as a rescue strategy for the clinical treatment of degenerative diseases. Until somatic cell nuclear transfer or induced pluripotent stem cell technology is further developed, human embryonic stem cells (hESC) have been considered a reliable source of specific cell types for cell-based therapy. The purpose of this study is to investigate whether hESC-derived neural stem cells (NSCs) can preserve vision when injected into the Royal College of Surgeons (RCS) rat -a retinal degeneration model.

Methods: : hESC-NSCs were generated by differentiation of hESC into NSCs with small molecules and chemically defined media. RCS rats received subretinal injections of NSCs (n=14) at postnatal (P) day 21; medium-injected (n=10) and untreated (n=10) animals were used as controls. Optokinetic responses and luminance thresholds were measured to test visual function at P60-150. Retinal immunohistochemistry was performed at the end of experiment.

Results: : hESC-NSC-treated eyes showed significantly better visual acuity than controls (0.52c/d versus 0.28c/d, p<0.001) at P90. Luminance threshold recordings from the superior colliculus detected much lower luminance thresholds in cell treated eyes compared with controls (0.4log units vs. 3.1log units P< 0.001). Correlated with functional preservation, substantial photoreceptor preservation (8 layers vs. a single layer) was observed in cell- treated retinas compared with controls. hESC-NSCs, identified with a human-specific antibody, were distributed in the subretinal space as a continuous layer, and were also identified within the inner retina. The injected hESC-NSCs were not found to express retinal cell markers; however, additional immunostaining correlated photoreceptor preservation with increased CD11b and FGF2 expression in the cell-injected eyes.

Conclusions: : hESC-NSCs can preserve vision after subretinal injection. The mechanism of hESC-NSC in protecting photoreceptors and visual function is partly through modifying retinal microglia responses, rather than differentiating into/replacing retinal neurons.

Keywords: transplantation • retinal degenerations: cell biology • neuroprotection 
×
×

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.

×