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Transplantation of rat embryonic stem cell-derived retinal cells restores visual function in the Royal College of Surgeons rats

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Abstract

Aim of study

To evaluate the feasibility of transplantation of embryonic stem cell (ESC)-derived retinal cells in the treatment of retinal degeneration.

Materials and methods

Rat ESCs were isolated and induced into retinal progenitor cells (RPCs) in vitro, which were subsequently induced into retinal pigment epithelium cells (RPEs) and photoreceptors (PRCs). All cells were identified by Western blot detection of their specific markers. RPEs and PRCs were, respectively, injected into the retina of Royal College of Surgeons (RCSs) rats. Control group was injected with PBS. Post-transplantation visual function was determined by electroretinography (ERG). The histology of the whole eye was compared by H&E staining.

Results

RPEs and PRCs were successfully derived from rat ESCs through the two-step differentiation as indicated by the presence of ESC- (Oct-3/4, Nanog, TRA-1-60 and TRA-1-81), RPC- (Rx, Mitf, Pax6 and Chx10), RPE- (RPE65 and keratin) and PRC-specific markers (blue opsin, red/green opsin, recoverin and rhodopsin) in Western blot. The amplitude of ERG a- and b-wave in RPE- and PRC-transplanted groups at week 2 and 10 after transplantation was markedly higher compared with PBS controls. Retinal injury and vascular stress response was not detected in any of the RCS rats after transplantation.

Conclusion

The developed stepwise protocol can derive retinal cells from ESCs. Transplantation of these retinal cells can restore visual function of RCS rats. Our study provides evidence for potential clinical application of ESC-based cell therapy for retinal degeneration.

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Acknowledgements

This study was supported by Scientific and Technological Landing Project of Higher Education in Jiangxi Province (12004044).

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Author notes

  1. Hongxi Wu and Jia Li have contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330000, China

    Hongxi Wu, Jia Li, Xinbang Mao, Guodong Li, Lin Xie & Zhipeng You

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  1. Hongxi Wu
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  2. Jia Li
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  3. Xinbang Mao
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  4. Guodong Li
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  5. Lin Xie
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Correspondence to Zhipeng You.

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The authors declare that they have no conflict of interest.

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Statement on the welfare of animals

This study was approved by the Research Ethics Committee at the Second Affiliated Hospital of Nanchang University, and was performed in strict accordance with the University's ethical standards.

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Wu, H., Li, J., Mao, X. et al. Transplantation of rat embryonic stem cell-derived retinal cells restores visual function in the Royal College of Surgeons rats. Doc Ophthalmol 137, 71–78 (2018). https://doi.org/10.1007/s10633-018-9648-8

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  • DOI: https://doi.org/10.1007/s10633-018-9648-8

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