Gene correction and transplantation into pathology model marmoset of iPS cells from retinitis pimentosa patient

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592616
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Saitama Medical University (2013); Keio University (2011-2012)
• Principal Investigator: YOSHIDA Tetsu 埼玉医科大学, 医学部, 助教 (00365438)
• Co-Investigator(Kenkyū-buntansha): OZAWA Yoko 慶應義塾大学, 医学部, 講師 (90265885)
• Project Period (FY): 2011 – 2013
• Keywords: 網膜色素変性症 / iPS細胞

Research Abstract

Retinitis pigmentosa (RP) is a kind of neurodegenerative diseases, which causes degeneration of rod cells in retina. In this work, we analyzed the mechanisms of the rod cells death and screened reagents which inhibited the degeneration. First of all, we developed a iPS cell line from an RP patient which a rhodopsin mutation and then induced rod cell differentiation. The rod cells with a rhodopsin mutation had more apoptotic cells than the cells without rhodopsin mutations. Next, we found that a reagent called 'rapamycin' inhibited the cell death of the rod cells, indicating that prescribing rapamycin to RP patient, which were caused by rhodopsin mutations, could inhibit the progress of the conditions of the disease.

Research Products

• [Journal Article] The use of induced pluripotent stem cells to reveal pathogenic gene mutations and explore treatments for retinitis pigmentosa (2014)
  • Author(s): Yoshida T, Ozawa Y, Suzuki K, Yuki K, Ohyama M, Akamatsu W, Matsuzaki Y, Shimmura S, Mitani K, Tsubota K, Okano H
  • Journal Title: Mol. Brain Volume: (in press)
  • Peer Reviewed
• [Journal Article] Neuroprotective Role of Superoxide Dismutase 1 in Retinal Ganglion Cells and Inner Nuclear layer Cells against N-methyl-D-aspartate -induced cytotoxicity (2013)
  • Author(s): Yuki K, Yoshida T, Miyake S, Tsubota K, Ozawa Y
  • Journal Title: Exp. Eye Res Volume: 115 Pages: 230-238
  • DOI: 10.1016/j.exer.2013.07.002
  • Peer Reviewed
• [Journal Article] Recovery from diabetes in neonatal mice after a low-dose streptozotocin treatment (2013)
  • Author(s): Kataoka M, Kawamuro Y, Shiraki N, Miki R, Sakano D, Yoshida T, Yasukawa T, Kume K, Kume S
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 430(3) Pages: 1103-1108
  • DOI: 10.1016/j.bbrc.2012.12.030
  • Peer Reviewed
• [Journal Article] Fate maps of ventral and dorsal pancreatic progenitor cells in early somite stage mouse embryos (2012)
  • Author(s): Miki R, Yoshida T, Murata K, Oki S, Kume K, Kume S
  • Journal Title: Mech. Dev Volume: 128 Pages: 597-609
  • DOI: 10.1016/j.mod.2011.12.004
  • Peer Reviewed
• [Journal Article] Generation of stratified squamous epithelial progenitor cells from mouse induced pluripotent stem cells (2011)
  • Author(s): Yoshida S, Yasuda M, Miyashita H, Ogawa Y, Yoshida T, Matsuzaki Y, Tsubota K, Okano H, Shimmura S
  • Journal Title: PLoS ONE Volume: 6(12) Pages: e28856
  • DOI: 10.1371/journal.pone.0028856
  • Peer Reviewed
• [Journal Article] Retinal ganglion cell loss in superoxide dismutase 1-deficiency (2011)
  • Author(s): Yuki K, Ozawa Y, Yoshida T, Kurihara T, Hirasawa M, Ozeki N, Shiba D, Noda K, Ishida S, Tsubota K
  • Journal Title: Invest. Ophthal. Vis. Sci Volume: 52(7) Pages: 4143-4150
  • DOI: 10.1167/iovs.10-6294
  • Peer Reviewed
• [Journal Article] Epiplakin1 marks the cholangiocyte lineage in normal liver and adult progenitors in injured liver (2011)
  • Author(s): Matsuo A, Yoshida T, Yasukawa T, Miki R, Ishikawa K, Fujiwara S, Kume K, Kume S
  • Journal Title: Gene Expr. Patterns Volume: 11(3-4) Pages: 255-262
  • DOI: 10.1016/j.gep.2011.01.001
  • Peer Reviewed
• [Presentation] iPS細胞を用いた網膜色素変性症における視細胞の変性機構の解析 (2013)
  • Author(s): 吉田哲、小沢洋子、鈴木啓一郎、平林由香、鈴木禎史、小泉春菜、結城賢弥、小林哲郎、大山学、天谷雅行、岡田洋平、赤松和土、松崎有未、三谷幸之介、榛村重人、坪田一男、岡野栄之
  • Organizer: 第12回日本再生医療学会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 20130321-23
• [Presentation] An analysis of the mechanisms of degradation of photoreceptor cells in a retinitis pigmentosa patient using iPS cells (2012)
  • Author(s): Tetsu Yoshida, Yoko Ozawa, Yuka Hirabayashi, Keiichiro Suzuki, Kohnosuke Mitani, Tetsuro Kobayashi, Manabu Ohyama, Masayuki Amagai, Yohei Okada, Wado Akamatsu, Kazuo Tsubota, Shigeto Shimmura, Hideyuki Okano
  • Organizer: International Society for Stem Cell Research (ISSCR) 10^<th> annual meeting
  • Place of Presentation: Pacifico Yokohama, Yokohama, Japan
  • Year and Date: 20120613-16
• [Presentation] A gene therapy for a gene mutation in human iPS cell using helper-dependent adenoviral vector (2011)
  • Author(s): T. Yoshida, H. Koizumi, K. Yuki, Y. Hirabayashi, K. Suzuki, K. Mitani, K. Tsubota, S. Shimmura, Y. Ozawa, H. Okano
  • Organizer: The Association for Research in Vision and Ophthalmology (ARVO) 2011, The Future of Eye and Vision Research
  • Place of Presentation: Fort Lauderdale, Florida, USA
  • Year and Date: 20110501-05