April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
RPE cells differentiated from human induced pluripotent stem cells show production of the visual chromophore and phagocytosis ability
Author Affiliations & Notes
  • Akiko Maeda
    Ophthalmology, Case Western Reserve Univ, Cleveland, OH
    Pharmacology, Case Western Reserve University, Cleveland, OH
  • Grazyna Palczewska
    Polgenix, Cleveland, OH
  • Hiroshi Maeno
    Ophthalmology, Case Western Reserve Univ, Cleveland, OH
  • Krzysztof Palczewski
    Pharmacology, Case Western Reserve University, Cleveland, OH
  • Masayo Takahashi
    RIKEN, Kobe, Japan
  • Tadao Maeda
    Ophthalmology, Case Western Reserve Univ, Cleveland, OH
  • Footnotes
    Commercial Relationships Akiko Maeda, None; Grazyna Palczewska, None; Hiroshi Maeno, None; Krzysztof Palczewski, None; Masayo Takahashi, None; Tadao Maeda, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1436. doi:
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    • Get Citation

      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)

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Abstract
 
Purpose
 

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.

 
Methods
 

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.

 
Results
 

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.

 
Conclusions
 

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.

 
Keywords: 687 regeneration • 701 retinal pigment epithelium • 695 retinal degenerations: cell biology  
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