July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Transplantation of human embryonic stem cell derived retinal tissue in the subretinal space of immunodeficient rats with retinal degeneration (RD)
Igor O Nasonkin; Bin Lin; Francois Binette; Gary Hogge; Robert Aramant; Ratnesh K. Singh; Magdalene J Seiler
Author Affiliations & Notes
  • Igor O Nasonkin
    Biotime, Inc., Alameda, California, United States
  • Bin Lin
    Physical Medicine & Rehabilitation; Ophthalmology, University of California, Irvine; School of Medicine, Irvine, California, United States
  • Francois Binette
    Biotime, Inc., Alameda, California, United States
  • Gary Hogge
    Biotime, Inc., Alameda, California, United States
  • Robert Aramant
    Physical Medicine & Rehabilitation; Ophthalmology, University of California, Irvine; School of Medicine, Irvine, California, United States
  • Ratnesh K. Singh
    Biotime, Inc., Alameda, California, United States
  • Magdalene J Seiler
    Physical Medicine & Rehabilitation; Ophthalmology, University of California, Irvine; School of Medicine, Irvine, California, United States
  • Footnotes
    Commercial Relationships   Igor Nasonkin, Biotime, Inc. (E); Bin Lin, None; Francois Binette, Biotime, Inc. (E); Gary Hogge, Biotime, Inc. (E); Robert Aramant, Ocular Transplantation LLC (P), Ocular Transplantation LLC (E); Ratnesh Singh, Biotime, Inc. (E); Magdalene Seiler, Ocular Transplantation LLC (P)
  • Footnotes
    Support  1R44EY027654-01A1
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3109. doi:
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      Igor O Nasonkin, Bin Lin, Francois Binette, Gary Hogge, Robert Aramant, Ratnesh K. Singh, Magdalene J Seiler; Transplantation of human embryonic stem cell derived retinal tissue in the subretinal space of immunodeficient rats with retinal degeneration (RD). Invest. Ophthalmol. Vis. Sci. 2019;60(9):3109.

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Abstract

Purpose : Human fetal retinal tissue has been successfully used for clinical trials to ameliorate vision in patients with severe retinal degenerative (RD) conditions. However, human fetal retinal tissue is controversial, hard to procure and insufficient to treat millions of blind people. Retinal tissue derived from human embryonic stem cells (hESCs) has both molecular and developmental characteristics similar to human fetal retina. Here, we investigate the survival of hESC-derived retinal tissue in the subretinal space of immunodeficient RD rats SD-Foxn1 Tg(S334ter)3Lav (RD nude), and Royal College of Surgeons (RCS nude).

Methods : Retinal organoids were derived from WA01(H1) hESC line (Singh et al., Stem Cells & Devel., 2015), with modifications. Immunohistochemistry was done to delineate the distribution of early retinal markers in retinal organoids.. Retinal tissue from organoids was placed into the subretinal space of immunodeficient RD rats (n=12 eyes RD nude) and n=2 (RCS nude rats) as described by Seiler and Aramant. The eyes were examined by fundoscopy and spectral domain optical coherence tomography (OCT) imaging.

Results : Preliminary transplantation studies done in immunodeficient rats showed overproliferation of grafts. After modification of retinal tissue derivation procedure, with focus on identifying clusters of differentiating retinal tissue from adherent monolayer cultures, we achieved the survival of hESC derived retinal tissue into the subretinal space of the rat eye without excessive proliferation.. OCT results showed the presence of grafts in the subretinal space. Further studies are underway to test the visual function of rats with subretinal hESC-3D retinal tissue grafts.

Conclusions : Careful in vitro selection of hESC-derived retinal tissue stops the overproliferation of grafts in the subretinal space of immunodeficient RD rats.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Copyright © 2024 Association for Research in Vision and Ophthalmology.
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