July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Co-transplantation of RPE and photoreceptors rescues vision in a mouse model of advanced retinal degeneration
Author Affiliations & Notes
  • Nikolaos Mitrousis
    Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
  • Sabiha Hacibekiroglu
    Lunenfeld-Tanenbaum Research Institute, University of Toronto, Toronto, Ontario, Canada
    Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
  • Katariina Mamia
    Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
  • Zhengyue Zhu
    Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
  • Beatrice Ballarin
    Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
  • Peter Poon
    Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada
  • Vallerie A. Wallace
    Opthalmology and Vision Science, Krembil Research Institute, University of Toronto, Toronto, Ontario, Canada
  • Yves Sauve
    Department of Ophtalmology, University of Alberta, Edmonton, Alberta, Canada
  • Andras Nagy
    Lunenfeld-Tanenbaum Research Institute, University of Toronto, Toronto, Ontario, Canada
  • Derek van der Kooy
    Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
    Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
  • Molly S. Shoichet
    Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada
    Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
  • Footnotes
    Commercial Relationships   Nikolaos Mitrousis, None; Sabiha Hacibekiroglu, None; Katariina Mamia, None; Zhengyue Zhu, None; Beatrice Ballarin, None; Peter Poon, None; Vallerie Wallace, None; Yves Sauve, None; Andras Nagy, None; Derek van der Kooy, None; Molly Shoichet, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3261. doi:
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      Nikolaos Mitrousis, Sabiha Hacibekiroglu, Katariina Mamia, Zhengyue Zhu, Beatrice Ballarin, Peter Poon, Vallerie A. Wallace, Yves Sauve, Andras Nagy, Derek van der Kooy, Molly S. Shoichet; Co-transplantation of RPE and photoreceptors rescues vision in a mouse model of advanced retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3261.

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

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Abstract

Purpose : Stem cell-based regenerative medicine is a novel and promising approach to overcome blindness, which has shown some potential in preclinical models of retinal disease lacking functional photoreceptors or retinal pigmented epithelium (RPE). However, in advanced stages of retinal degeneration both RPE and photoreceptors are compromised, and replacement of both cell types would be required to re-establish vision. Here, we validated a mouse model of advanced retinal degeneration and used it to test the hypothesis that co-transplanting RPE and photoreceptors can lead to enhanced visual recovery as compared to either of those cell types alone.

Methods : We used NaIO3 (70 mg/kg) to induce retinal degeneration in mice. The temporal onset of blindness was validated by optokinetic head tracking (OKT) and light avoidance assays, while tissue histology confirmed the eradication of RPE and significant degeneration of photoreceptors. We isolated rod photoreceptors by cell sorting from P6 NrlGFP mice and derived RPE from human embryonic stem cells following the Lanza protocol. The cells were transplanted subretinally after the onset of complete blindness, using a hyaluronic acid-based hydrogel as a vehicle. OKT, light-avoidance and electroretinography (ERG) were performed to assess visual function after transplantation. Statistical comparisons were made using ANOVA.

Results : We found that a single 70 mg/kg dose of NaIO3 was sufficient to induce complete blindness in 1 month. No significant visual recovery was detected in the groups transplanted with vehicle, photoreceptors alone or RPE alone. The co-transplant group exhibited significant (p<0.05) visual recovery by both OKT and light avoidance assays 4 weeks after transplantation. The co-transplant group displayed detectable scotopic b-waves, while the vehicle and individual cell type groups had extinguished ERGs.

Conclusions : Co-transplanting RPE and photoreceptors can lead to some visual recovery in a completely blind animal model of advanced retinal degeneration. These results corroborate the hypothesis that both cell types should be replaced in a degenerated retina to achieve optimal function. The specific molecular mechanism underlying our behavioral results warrants further investigation.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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