Research: MAEDA and COLLEAGUES,

Listed in Issue 240

Abstract

MAEDA and COLLEAGUES,  (1)From the Departments of Ophthalmology and Visual Sciences, investigating potential treatment options for retinal degenerative diseases, studied the expression of functional visual cycle enzymes in human induced pluripotent stem (hiPS) cells compared with primary pigmented epithelial (RPE) cells from mice.

Background

Differentiated retinal pigmented epithelial (RPE) cells have been obtained from human induced pluripotent stem (hiPS) cells. However, the visual (retinoid) cycle in hiPS-RPE cells has not been adequately examined.

Methodology

Here the authors determined the expression of functional visual cycle enzymes in hiPS-RPE cells compared with that of isolated wild-type mouse primary RPE (mpRPE) cells in vitro and in vivo.

Results

hiPS-RPE cells appeared morphologically similar to mpRPE cells. Notably, expression of certain visual cycle proteins was maintained during cell culture of hiPS-RPE cells, whereas expression of these same molecules rapidly decreased in mpRPE cells. Production of the visual chromophore, 11-cis-retinal, and retinosome formation also were documented in hiPS-RPE cells in vitro. When mpRPE cells with luciferase activity were transplanted into the subretinal space of mice, bioluminance intensity was preserved for >3 months. Additionally, transplantation of mpRPE into blind Lrat(-/-) and Rpe65(-/-) mice resulted in the recovery of visual function, including increased electrographic signalling and endogenous 11-cis-retinal production. Finally, when hiPS-RPE cells were transplanted into the subretinal space of Lrat(-/-) and Rpe65(-/-) mice, their vision improved as well. Moreover, histological analyses of these eyes displayed replacement of dysfunctional RPE cells by hiPS-RPE cells.

Conclusion

Together, our results show that hiPS-RPE cells can exhibit a functional visual cycle in vitro and in vivo. These cells could provide potential treatment options for certain blinding retinal degenerative diseases.

References

Maeda T(1), Lee MJ, Palczewska G, Marsili S, Tesar PJ, Palczewski K, Takahashi M, Maeda A. Retinal pigmented epithelial cells obtained from human induced pluripotent stem cells possess functional visual cycle enzymes in vitro and in vivo. J Biol Chem. 288(48):34484-93. Nov 29 2013. doi: 10.1074/jbc.M113.518571. Epub Oct 15 2013.

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