September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Transplantation of human induced pluripotent stem cell-derived retinal tissue in primate models of retinal degeneration with perimetric analysis
Author Affiliations & Notes
  • Hiroshi Shirai
    Retinal Regeneration, Riken center for developmental biology, Kobe, Japan
    Ophthalmology, Nagoya University, Nagoya, Japan
  • Michiko Mandai
    Retinal Regeneration, Riken center for developmental biology, Kobe, Japan
  • Masaharu Kinoshita
    Hirosaki University, Hirosaki, Japan
  • Hirotaka Onoe
    Functional Probe Research Laboratory, Riken center for developmental biology, Kobe, Japan
  • Keizo Matsushita
    Retinal Regeneration, Riken center for developmental biology, Kobe, Japan
    Regenerative and Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd., Kobe, Japan
  • Atsushi Kuwahara
    Regenerative and Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd., Kobe, Japan
    Neurogenesis and Organogenesis Group, Riken center for developmental biology, Kobe, Japan
  • Suguru Yamasaki
    Retinal Regeneration, Riken center for developmental biology, Kobe, Japan
    Regenerative and Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd., Kobe, Japan
  • Hiroko Terasaki
    Ophthalmology, Nagoya University, Nagoya, Japan
  • Yoshiki Sasai
    Neurogenesis and Organogenesis Group, Riken center for developmental biology, Kobe, Japan
  • Masayo Takahashi
    Retinal Regeneration, Riken center for developmental biology, Kobe, Japan
  • Footnotes
    Commercial Relationships   Hiroshi Shirai, None; Michiko Mandai, None; Masaharu Kinoshita, None; Hirotaka Onoe, None; Keizo Matsushita, None; Atsushi Kuwahara, None; Suguru Yamasaki, None; Hiroko Terasaki, None; Yoshiki Sasai, None; Masayo Takahashi, None
  • Footnotes
    Support   Research Center Network for Realization of Regenerative Medicine (AMED)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5319. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Hiroshi Shirai, Michiko Mandai, Masaharu Kinoshita, Hirotaka Onoe, Keizo Matsushita, Atsushi Kuwahara, Suguru Yamasaki, Hiroko Terasaki, Yoshiki Sasai, Masayo Takahashi; Transplantation of human induced pluripotent stem cell-derived retinal tissue in primate models of retinal degeneration with perimetric analysis. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5319.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Retinal transplantation therapy for retinitis pigmentosa is increasingly of interest. We investigated the competency of human induced pluripotent stem cell-derived retinal tissue (hiPSC-retina) following transplantation into primate model of retinal degeneration. We also tried perimetric studies with an eye of retinal degeneration model in purpose of evaluating functional restoration after retinal transplantation.

Methods : hiPSC-retina of differentiation day (DD) 63 was transplanted into the laser photocoagulated retina of a cynomolgus monkey, and the monkey was sacrificed for immunohistological analysis at graft age of DD282 following in vivo imaging. A rhesus monkey was trained to perform perimetric analysis, and visual field defect was investigated after focal laser photocoagulation.

Results : OCT imaging demonstrated the presence of graft retina-like sheets in regions where the host ONL was substantially degenerated. Photoreceptors in the graft were observed to form rosette-like structures. FA revealed no evidence of rejection. All the rosettes were positive for recoverin, rhodopsin, and cone opsins, indicating terminal photoreceptor maturation. No proliferating (Ki67-positive) cells were observed in rosettes. Photoreceptor cells, co-expressing human markers and recoverin, were found to be in contact with host bipolar dendrites. We next successfully detected focal visual field loss in the corresponding area after laser photocoagulation, which was never observed before injury. Transplantation of hiPSC-retina was safely done in the photocoagulated area.

Conclusions : We demonstrated that the graft could survive, mature, and possibly integrate with host bipolar cells in the eye of the monkey model. With successful detection of visual field defect in the photoreceptor degenerating retina and transplantation within the degeneration site, we intend to monitor light perception of the graft area.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×