July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Transplantation of embryonic stem cell-derived retinal neurons preserves retinal ganglion cells and their function in glaucomatous mice
Author Affiliations & Notes
  • Karen Chang
    Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Kin-Sang Cho
    Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • sangbae Kim
    HGSC, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Chenmei Luo
    Astellas Institute of Regenerative Medicine, Marlborough, Massachusetts, United States
  • Wei-Fang Su
    Department of Materials Science and Engineering, National Taiwan University, Taipei, Taiwan
  • Rui Chen
    HGSC, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Maria Mirotsou
    Astellas Institute of Regenerative Medicine, Marlborough, Massachusetts, United States
  • Robert Lanza
    Astellas Institute of Regenerative Medicine, Marlborough, Massachusetts, United States
  • Dong Feng Chen
    Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Min-Huey Chen
    School of Dentistry, National Taiwan University, Thailand
  • Footnotes
    Commercial Relationships   Karen Chang, None; Kin-Sang Cho, Astellas Pharma US (F); sangbae Kim, None; Chenmei Luo, Astellas Pharma US (E); Wei-Fang Su, None; Rui Chen, None; Maria Mirotsou, Astellas Pharma US (E); Robert Lanza, Astellas Pharma US (E); Dong Chen, Astellas Pharma US (F); Min-Huey Chen, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2893. doi:https://doi.org/
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      Karen Chang, Kin-Sang Cho, sangbae Kim, Chenmei Luo, Wei-Fang Su, Rui Chen, Maria Mirotsou, Robert Lanza, Dong Feng Chen, Min-Huey Chen; Transplantation of embryonic stem cell-derived retinal neurons preserves retinal ganglion cells and their function in glaucomatous mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2893. doi: https://doi.org/.

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

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Abstract

Purpose : The regeneration ability of adult mature nervous system is limited. As part of the central nervous system (CNS), retinal ganglion cells and the optic nerve are incapable of regenerating once the damage occurs, which results in permanent vision loss. This study proposes to restore or re-establish the functions of retinal ganglion cells (RGCs) in glaucomatous mice by transplanting embryonic stem cell-derived retinal neurons (SRNs).

Methods : The SRNs were derived from human embryonic stem cells (hESCs) following a defined procedure. RNA sequencing (RNA-Seq) analysis was employed to determine the gene expression profile of SRNs. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to further characterize and verify the expression of specific cell markers. Glaucoma was induced in mice by anterior chamber injection of microbeads. SRNs transplantation was performed intravitreally the day after MB injection. The percentage of RGC loss and RGC function were examined at 4 and 8 weeks post SRN transplantation.

Results : RNA-seq analysis revealed large similarity of hESC-derived RSNs with human amacrine cells, but were distinct from any other retinal cell types. Results of RT-PCR and immunohistochemistry demonstrated their expression of neuronal marker, Neurofilament. Transplantation of RSNs supported RGC survival in glaucomatous mice. Results of positive Scotopic Threshold Response (pSTR) also showed improvement of retinal function after 4 weeks of transplantation. Transplanted cells expressed neuronal marker Tuj-1 and extended long neurites when integrating into the host retina. Some transplanted cells made synaptic connections with neurons of the host retina.

Conclusions : Human embryonic stem cells can be differentiated into amacrine-like cells. Transplantation of ESC-derived amacrine-like cells into the retina protects host RGCs from glaucomatous degeneration, and prevents RGC functional loss in mice. Our long-term goal is to apply this feasible cell therapy for optic nerve restoration and regeneration in patients with glaucoma.

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

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