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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)
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.
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.
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.
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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