April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Human iPSC-derived neural progenitor cells preserve vision in a rat retinal degeneration model
Author Affiliations & Notes
  • YuChun Tsai
    Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, CA
  • Bin Lu
    Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, CA
  • Sergey Girman
    Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, CA
  • Benjamin Bakondi
    Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, CA
  • Melissa Kaye Jones
    Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, CA
  • Anais Sahabian
    Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, CA
  • Dhruv Sareen
    Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, CA
  • Clive Svendsen
    Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, CA
  • Shaomei Wang
    Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, CA
  • Footnotes
    Commercial Relationships YuChun Tsai, None; Bin Lu, None; Sergey Girman, None; Benjamin Bakondi, None; Melissa Jones, None; Anais Sahabian, None; Dhruv Sareen, None; Clive Svendsen, None; Shaomei Wang, None
  • Footnotes
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Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3978. doi:https://doi.org/
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      YuChun Tsai, Bin Lu, Sergey Girman, Benjamin Bakondi, Melissa Kaye Jones, Anais Sahabian, Dhruv Sareen, Clive Svendsen, Shaomei Wang; Human iPSC-derived neural progenitor cells preserve vision in a rat retinal degeneration model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3978. doi: https://doi.org/.

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

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Abstract

Purpose: Neural progenitor cells (NPCs) have been shown effective in treating degenerative neurological disorders including retinal degeneration. Induced pluripotent stem cell (iPSC) therapies are gaining momentum for regenerative medicine. An ideal cell type to treat retinal degeneration should be offering great preservation of vision, renewable, no ethical concern, not causing immune rejection. Here we study human NPC derived from iPSC (iNPCs) in preserving vision after transplantation into the Royal College Surgeon (RCS) rat, a well-established model for retinal degeneration.

Methods: Non-integrating human iPSCs were generated using Yamanaka episomal plasmids from an Amaxa human dermal fibroblast nucleofector kit. NPCs were derived from iPSC-EZ spheres according to Sareen et al., 2013. iNPCs or medium were injected into the subretinal space of RCS rats at 21 days postnatal (P21). Visual functions were evaluated using Optokinetic response (OKR), electroretinography (ERG), and luminance threshold recordings (LTR) from superior colliculus. Histological examination of the retinas was performed by light, confocal, and electron microscopy. The in vitro phagocytosis assay of photoreceptor outer segments (POS) by iNPCs was examined by RT-PCR, flow cytometry, immunocytochemistry, and western blot after feeding naïve or FITC labeled POS.

Results: At P90-100, iNPCs treated eyes sustained near normal visual functions and retinal integrity compared with controls. Donor cells showed extensive migration from the injection site, formation of a continuous layer in the subretinal space, and limited distribution in the inner retina. In cell treated eyes, the debris zone was significantly diminished, suggesting the involvement of phagocytosis. iNPCs are capable of phagocytosing POS in vitro in a time and dose dependent manner, and express transcripts associated with RPE-specific phagocytosis, including Mer Tyrosine Kinase (MERTK).

Conclusions: The results underscore the potential therapeutic utility of iNPCs for age-related macular degeneration and other degenerative retinal diseases.

Keywords: 412 age-related macular degeneration • 721 stem cells • 645 phagocytosis and killing  
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