Transplantation of reprogrammed embryonic stem cells improves visual function in a mouse model for retinitis pigmentosa

Nan Kai Wang, Joaquin Tosi, Jennifer Mie Kasanuki, Chai Lin Chou, Jian Kong, Nancy Parmalee, Katherine J. Wert, Rando Allikmets, Chi Chun Lai, Chung Liang Chien, Takayuki Nagasaki, Chyuan Sheng Lin, Stephen H. Tsang

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Background. To study whether C57BL/6J-Tyr/Jc-2 (C2J) mouse embryonic stem (ES) cells can differentiate into retinal pigment epithelial (RPE) cells in vitro and then restore retinal function in a model for retinitis pigmentosa: Rpe65rd12/Rpe65rd12 C57BL6 mice. Methods. Yellow fluorescent protein (YFP)-labeled C2J ES cells were induced to differentiate into RPE-like structures on PA6 feeders. RPE-specific markers are expressed from differentiated cells in vitro. After differentiation, ES cell-derived RPE-like cells were transplanted into the subretinal space of postnatal day 5 Rpe65rd12/Rpe65rd12 mice. Live imaging of YFP-labeled C2J ES cells demonstrated survival of the graft. Electroretinograms (ERGs) were performed on transplanted mice to evaluate the functional outcome of transplantation. Results. RPE-like cells derived from ES cells sequentially express multiple RPE-specific markers. After transplantation, YFP-labeled cells can be tracked with live imaging for as long as 7 months. Although more than half of the mice were complicated with retinal detachments or tumor development, one fourth of the mice showed increased electroretinogram responses in the transplanted eyes. Rpe65rd12/Rpe65rd12 mice transplanted with RPE-like cells showed significant visual recovery during a 7-month period, whereas those injected with saline, PA6 feeders, or undifferentiated ES cells showed no rescue. Conclusions. ES cells can differentiate, morphologically, and functionally, into RPE-like cells. Based on these findings, differentiated ES cells have the potential for the development of new therapeutic approaches for RPE-specific diseases such as certain forms of retinitis pigmentosa and macular degeneration. Nevertheless, stringent control of retinal detachment and teratoma development will be necessary before initiation of treatment trials.

Original languageEnglish (US)
Pages (from-to)911-919
Number of pages9
Issue number8
StatePublished - Apr 2010
Externally publishedYes


  • Embryonic stem cell
  • RPE65
  • Retinal degeneration
  • Retinal pigment epithelium

ASJC Scopus subject areas

  • Transplantation


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