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Akiko Maeda, Grazyna Palczewska, Hiroshi Maeno, Krzysztof Palczewski, Masayo Takahashi, Tadao Maeda; RPE cells differentiated from human induced pluripotent stem cells show production of the visual chromophore and phagocytosis ability. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1436.
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© ARVO (1962-2015); The Authors (2016-present)
The visual (retinoid) cycle activity in human iPS derived RPE (hiPS-RPE) cells has not been fully examined. We examined the ability for production of visual chromophore, 11-cis-retinal, in hiPS-RPE cells. We also examined their phagocytosis ability.
hiPS-RPE cells and mouse primary RPE (mpRPE) cells were examined their expression of visual cycle enzymes and ability for generation of 11-cis-retinal in vitro and in vivo. In addition to hiPS-RPE and mpRPE cells, ARPE19 cells and macrophage cell line were also used for study of phagocytosis.
hiPS-RPE cells appeared morphologically similar to mpRPE cells. 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 11-cis-retinal and retinosome formation were documented in hiPS-RPE cells in vitro. Transplantation of mpRPE into blind Lrat-/- and Rpe65-/- mice resulted in the recovery of visual function, including increased electrographic signaling and endogenous 11-cis-retinal production. 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. hiPS-RPE cells also display good expression of phagocytosis markers including MERTK and some phagocytosis ability.
Our results show that hiPS-RPE cells can exhibit a functional visual cycle and phagocytosis. These cells could provide potential treatment options for certain blinding retinal degenerative diseases.
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