May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Transplantation of Eye-Like Structures Differentiated From ES Cells in vitro and the Resultant Regeneration of Retinal Ganglion Cells in vivo
Author Affiliations & Notes
  • H. Aoki
    Gifu University Graduate School of Medicine, Gifu, Japan
    Tissue and Organ Development,
  • A. Hara
    Gifu University Graduate School of Medicine, Gifu, Japan
    Tumor Pathology,
  • M. Niwa
    Gifu University Graduate School of Medicine, Gifu, Japan
    Medical Eucation Development Center,
  • T. Suzuki
    Ophthalmology, Ehime University School of Medicine, Ehime, Japan
  • T. Kunisada
    Gifu University Graduate School of Medicine, Gifu, Japan
    Tissue and Organ Development,
  • Footnotes
    Commercial Relationships H. Aoki, None; A. Hara, None; M. Niwa, None; T. Suzuki, None; T. Kunisada, None.
  • Footnotes
    Support the Ministry of Health, Welfarel nd Labor of Japan
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 4104. doi:
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    • Get Citation

      H. Aoki, A. Hara, M. Niwa, T. Suzuki, T. Kunisada; Transplantation of Eye-Like Structures Differentiated From ES Cells in vitro and the Resultant Regeneration of Retinal Ganglion Cells in vivo. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4104.

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

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Abstract

Purpose:: A culture system to generate eye-like structures consisting of lens, neural retina, and retinal pigmented epithelium cells from undifferentiated mouse embryonic stem (mES) cells has been established. When these eye-like structures were transplanted in chick embryo to test the potential of their integration into developing ocular tissue, they could develop into lens or neuronal protein marker expressing cell clusters in host retina. Likewise when RPE cells derived from eye-like structures were transplanted, they were capable of populating the developing chick eye as a part of the single cell layer of mature RPE cells. The aim of this study was to investigate the potential of these eye-like structures as a means of establishing an in vivo therapy model for the regeneration of ganglion cells in an injured retina.

Methods:: mES cells were induced to differentiate into eye-like structures in vitro for 11 days. They were transplanted into the vitreous cavity of adult mouse eye administered with or without NMDA prior to transplantation to specifically induce injury to the ganglion cell layer. Eyes were analyzed by immunohistochemistry 10 days after transplantation.

Results:: Transplanted eye-like structures integrate into the ganglion cell layer and differentiate into neurons. While they rarely express ganglion cell markers, when transplanted into NMDA-treated retinas, these cells spread on the surface of the retina and cover a relatively larger area. It was noteworthy that these ES-derived eye cells frequently differentiated into cells expressing ganglion cell-specific markers and formed a new ganglion cell layer in NMDA-treated aganglionic retinas. Moreover, some of them were observed to extend their axons into the optic papillae of the host.

Conclusions:: ES cell-derived eye-like structures contain cell populations that can differentiate into not only retinal pigmented epithelium cells and lens but also retinal ganglion-like cells in vivo. Moreover they regenerated to form a new ganglion cell layer and also shown to have the potential to integrate into the optic nerve in vivo. These findings suggest that cells prepared from the eye-like structures generated from ES cells in vitro may be used in cell replacement treatments and may also serve as a therapy model for glaucoma in vivo.

Keywords: differentiation • ganglion cells • transplantation 
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