June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Deterioration of Phagocytosis in induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelial Cells established from Patients with Retinitis Pigmentosa Carrying Mer Tyrosine Kinase Mutations
Author Affiliations & Notes
  • Miho Tagawa
    Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Japan
  • Hanako Ikeda
    Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Japan
  • Yumi Inoue
    Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Japan
  • Sachiko Iwai
    Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Japan
  • Yuto Iida
    Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Japan
  • Masayuki Hata
    Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Japan
  • Isao Asaka
    Center for iPS Cell Research and Application (CiRA), Kyoto Daigaku, Kyoto, Japan
  • Akitaka Tsujikawa
    Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Japan
  • Footnotes
    Commercial Relationships   Miho Tagawa, None; Hanako Ikeda, Alcon Japan (F), Alcon Pharma (R), Eisai (R), Kyoto Drug Discovery & Development (F), Kyoto Drug Discovery & Development (C), Kyoto Drug Discovery & Development (P), Novartis Pharma (F), Novartis Pharma (R), ONO RHARMACEUTICAL. CO (R), Santen (R), Senju Pharmacentical (R); Yumi Inoue, None; Sachiko Iwai, None; Yuto Iida, None; Masayuki Hata, None; Isao Asaka, None; Akitaka Tsujikawa, Alcom Pharma (R), Alcon Japan (F), Alcon Japan (R), Alcon Pharna (F), AMO Japan (F), AMO Japan (R), Bayer Yakuhin (R), Canon (F), Canon (R), Findex (F), Kowa Pharmacentical (F), Kowa Pharmacentical (R), Novartis Pharma (R), Otsuka Pharmacentical (F), Otuska Pharmacentical (R), Pfizer (F), Pfizer (R), Santen (R), Santen Pharmacentical (F), Sanwa Kagaku Kenkyusha (R), Senju Pharmacentical (F), Senju Pharmacentical (R), Taiho Pharma (F), Wakamoto Pharmacentical (F), Wakamoto Pharmacentical (R)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2951. doi:
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      Miho Tagawa, Hanako Ikeda, Yumi Inoue, Sachiko Iwai, Yuto Iida, Masayuki Hata, Isao Asaka, Akitaka Tsujikawa; Deterioration of Phagocytosis in induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelial Cells established from Patients with Retinitis Pigmentosa Carrying Mer Tyrosine Kinase Mutations. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2951.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To investigate the mechanism of onset and progression of retinitis pigmentosa (RP) due to mutations in Mer tyrosine kinase (MERTK) gene using induced pluripotent stem cells of the retinal pigment epithelium (iPSC-RPE) derived from patients.

Methods : iPSC-RPE were derived from two patients with RP with MERTK gene mutations (MTK) and three normal (NOR) individuals. Morphological differences in the diseased (MTK) and normal (NOR) iPSC-RPE were evaluated using bright field microscopy, transmission electron microscopy, and immunochemistry analyses. Phagocytosis was analyzed with fluorescent bovine photoreceptor outer segments (POS) using flow cytometry and POS-derived protein, rhodopsin, in the iPSC-RPE cells fed POS using western blotting.

Results : There were no morphological differences between MTK and NOR iPSC-RPE. Flow cytometry analysis revealed that the percentage of FITC-positive MTK iPSC-RPE (15.5 ± 6.6 %) was significantly lower (P = 0.046) than that of NOR iPSC-RPE (27.3 ± 14.2 %). The relative intensity of rhodopsin in MTK iPSC-RPE (0.51 ± 0.18) was significantly lower (P = 0.016) than that in NOR iPSC-RPE (0.82 ± 0.20).

Conclusions : We successfully developed a human cell-based in vitro model of retinal degeneration. In the diseased iPSC-RPE, phagocytosis of POS was found to be deteriorated.

This is a 2021 ARVO Annual Meeting abstract.

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