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N.-K. Wang, J. Tosi, C. Chou, J. Kong, K. Wert, R. Allikmets, C.-C. Lai, T. Nagasaki, C.-S. Lin, S. H. Tsang; Transplantation of Reprogrammed Embryonic Stem Cells Improves Visual Function in a Mouse Model for Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6328.
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© ARVO (1962-2015); The Authors (2016-present)
To study if C57BL/6J-Tyrc-2j/J (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.
Yellow fluorescent protein (YFP)-labeled C2J ES cells were induced to differentiate into RPE-like structures on PA6 feeders. Immunoblots were used to determine expression of RPE-specific markers from in vitro differentiated cells. 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 was carried out to determine the survival of the graft. Electroretinograms (ERGs) were performed on transplanted mice to evaluate the functional outcome of transplantation.
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 ERG responses in the transplanted eyes. Rpe65rd12/Rpe65rd12 mice transplanted with RPE-like cells showed significant visual recovery over a 7-month period, while those injected with saline, PA6 feeders or undifferentiated ES cells showed no rescue.
ES cells have the potential to 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.
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