July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
A Complete Retina Patch to Treat Irreversible Retinal Injuries
Author Affiliations & Notes
  • Biju Thomas
    Ophthalmology, USC Eye Institute, Los Angeles, California, United States
    Institute for Biomedical Therapeutics, USC, Los Angeles, California, United States
  • Bryce T McLelland
    Physical Medicine & Rehabilitation, UC Irvine School of Medicine, Irvine, California, United States
  • Danhong Zhu
    Pathology, USC, Los Angeles, California, United States
  • Gabriel Nistor
    AIVITA Biomedical, Irvine, California, United States
  • Robert B Aramant
    Physical Medicine & Rehabilitation, UC Irvine School of Medicine, Irvine, California, United States
  • David R Hinton
    Pathology, USC, Los Angeles, California, United States
  • Mark S. Humayun
    Ophthalmology, USC Eye Institute, Los Angeles, California, United States
    Institute for Biomedical Therapeutics, USC, Los Angeles, California, United States
  • Hans S Keirstead
    AIVITA Biomedical, Irvine, California, United States
  • Magdalene J Seiler
    Physical Medicine & Rehabilitation, UC Irvine School of Medicine, Irvine, California, United States
  • Footnotes
    Commercial Relationships   Biju Thomas, None; Bryce McLelland, None; Danhong Zhu, None; Gabriel Nistor, AIVITA Biomedical (E); Robert Aramant, Ocular Transplantation LLC (P), Ocular Transplantation LLC (E); David Hinton, RPT (P); Mark Humayun, RPT (P); Hans Keirstead, AIVITA Biomedical (S), AIVITA Biomedical (E); Magdalene Seiler, Ocular Transplantation LLC (P)
  • Footnotes
    Support  CIRM Disc 1 (BBT), CIRM DT1 (MSH), CIRM TR4-06648 (MJS), NIH R01EY024045 (HSK), Bright Focus Foundation (BBT)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 558. doi:
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    • Get Citation

      Biju Thomas, Bryce T McLelland, Danhong Zhu, Gabriel Nistor, Robert B Aramant, David R Hinton, Mark S. Humayun, Hans S Keirstead, Magdalene J Seiler; A Complete Retina Patch to Treat Irreversible Retinal Injuries. Invest. Ophthalmol. Vis. Sci. 2018;59(9):558.

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

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Abstract

Purpose : To develop a cellular therapy for irreversible eye injuries by co-grafting polarized retinal pigment epithelium (RPE) supported by an artificial Bruch’s membrane (ultrathin parylene), together with sheets of retina organoids (RO) that will mature into photoreceptors and other retinal cells.

Methods : The CSC14 (AIVITA Biomedical; NIH registry 0284) and the H9 derived CRX-GFP expressing hESC cell lines (Collin et al. 2016, Stem Cells 34:311–321) were used to differentiate retina organoids (modified after the protocol of Zhong et al 2014). hESCs at 80% confluency are aggregated to embryoid bodies (EBs). From day 21-38, eye field (“horseshoe”) structures are cut out and the resulting retinal spheres (containing retinal progenitors and RPE) are maintained in suspension culture (d30 – 93). For the preparation of RPE implants, H9 hESC were cultured and spontaneously differentiated to RPE cells. The hESC-RPE obtained from the primary cultures were isolated and further cultured. Passage 3 of hESC-RPE were seeded and cultured around 30 days on ultrathin parylene substrates to produce polarized monolayer RPE implants. For the preparation of hESC-RPE+RO co-grafts, RO sheets were dissected out and combined with RPE implants with the help of suitable bio-adhesive agents. Matrigel, gelatin and alginate were tested in 7 different embedding trials. The co-grafts were surgically placed into the subretinal (SR) space of immunodeficient Royal College of Surgeon (RCS) rats (46-55 day old males and females, n=5). Implant placement was evaluated by Optical Coherence Tomography (OCT). Histological assessments were performed using H&E staining and immunohistochemistry.

Results : Retina co-grafts can be prepared by combining RPE implants and RO sheets. Alginate appeared to have the best adhesive properties and provided gentle encapsulation. Successful surgical implantation of the co-grafts into the SR space of immunodeficient RCS rats is demonstrated by OCT imaging. Histological evaluation confirmed the survival of the co-grafts and maintenance of its laminar structure until the end of the experimental period (up to 1 month post-implantation).

Conclusions : The study supports our ability to combine RPE+RO into a co-graft that can be surgically placed into the rat’s SR area. This novel tissue engineering technique can enable replacement of an area of a diseased retina.

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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