June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Improving the restoration of visual function in RCS rats by transplanting a monolayer of RPE cells derived from human embryonic stem cells
Author Affiliations & Notes
  • Karim BEN M'BAREK
    INSERM UMR861, I-Stem, AFM, Evry, France
    UEVE UMR861, I-Stem, AFM,, Evry, France
  • Walter Habeler
    INSERM UMR861, I-Stem, AFM, Evry, France
    UEVE UMR861, I-Stem, AFM,, Evry, France
  • Alexandra Plancheron
    INSERM UMR861, I-Stem, AFM, Evry, France
    UEVE UMR861, I-Stem, AFM,, Evry, France
  • Mohamed Jarraya
    Human Tissue Bank, Saint-Louis Hospital, Paris, France
  • Ying Yang
    Institut de la Vision, INSERM U968 ; Sorbonne Universités, UPMC-Paris 06 ; CNRS UMR7210,, Paris, France
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts,, Paris, France
  • José-Alain Sahel
    Institut de la Vision, INSERM U968 ; Sorbonne Universités, UPMC-Paris 06 ; CNRS UMR7210,, Paris, France
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts,, Paris, France
  • Marc Peschanski
    INSERM UMR861, I-Stem, AFM, Evry, France
    UEVE UMR861, I-Stem, AFM,, Evry, France
  • Olivier Goureau
    Institut de la Vision, INSERM U968 ; Sorbonne Universités, UPMC-Paris 06 ; CNRS UMR7210,, Paris, France
  • Christelle Monville
    INSERM UMR861, I-Stem, AFM, Evry, France
    UEVE UMR861, I-Stem, AFM,, Evry, France
  • Footnotes
    Commercial Relationships Karim BEN M'BAREK, None; Walter Habeler, None; Alexandra Plancheron, None; Mohamed Jarraya, None; Ying Yang, None; José-Alain Sahel, None; Marc Peschanski, None; Olivier Goureau, None; Christelle Monville, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1833. doi:
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      Karim BEN M'BAREK, Walter Habeler, Alexandra Plancheron, Mohamed Jarraya, Ying Yang, José-Alain Sahel, Marc Peschanski, Olivier Goureau, Christelle Monville; Improving the restoration of visual function in RCS rats by transplanting a monolayer of RPE cells derived from human embryonic stem cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1833.

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

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Abstract

Purpose: Replacement of defective retinal pigment epithelium (RPE) by RPE cells derived from human pluripotent stem cells provide a novel approach to a rational treatment of forms of blindness that affect the RPE. Transplantation of a polarized RPE monolayer as a sheet seems to be more promising than injection of RPE cell suspension. We recently developed a tissue-engineered product (TEP) consisting of RPE cells derived from human Embryonic Stem (hES) cells disposed on a biocompatible substrate (denuded human amniotic membrane). Here, we have compared the visual recovery of RCS rats after transplantation of RPE cells in suspension vs. TEP.

Methods: RCS rats (N=47) were grafted at day 28 postnatal (P28) with either a cell suspension of RPE cells, or the TEP. Photoreceptor functionality and survival were evaluated at different times (from P60 to P118) after transplantation through electroretinography (ERG) and optokinetic tests.

Results: We successfully developed a surgical procedure to graft the TEP in the subretinal space of P28 RCS rats by wrapping the TEP in a thin gelatin layer. We demonstrated by measuring the b wave amplitude after 72 days (P90 rats) that TEP engraftment provide better ERG responses (198.9±29.4μV) compared to the cell suspension injection (95.8±67.7μV; p=0.0001) and dystrophic control (30.1±25.0μV; p=0.0001). Visual acuity evaluated through optokinetic responses in P118 RCS rats indicate that, compared to the SHAM (gelatin alone, 0.268±0.104c/d), injection of RPE cell suspension (0.444±0.093c/d; p=0.001) or TEP (0.496±0.085c/d; p<0.0001) improved performance of dystrophic eyes.

Conclusions: Our optokinetic test results indicate that injection of hES-derived RPE cells as a cell suspension or as a monolayer (TEP) ameliorate the functionality and/or the survival of photoreceptors in transplanted RCS rats. ERG recording clearly demonstrated that TEP engraftment leads to a better visual improvement in RCS rats, and that this recovery was maintained for a longer period of time. Further morphologic and histologic studies are ongoing to assess the effect of transplanted cells on host photoreceptor degeneration.

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