再生に向けたヒト人工多能性幹細胞を用いた網膜変性疾患の病態解明

2010 Fiscal Year Annual Research Report

• Project/Area Number: 21592265
• Research Institution: Keio University
• Principal Investigator: 小沢 洋子 慶應義塾大学, 医学部, 講師 (90265885)
• Keywords: 網膜 / 視細胞 / 再生 / iPS / 神経保護

Research Abstract

再生に向けたヒト人工多能性幹(iPS)細胞を用いた網膜変性疾患の病態解析をするために、申請者の研究室でもiPS細胞からの網膜細胞への分化誘導系を立ち上げた。浮遊培養と接着培養を組み合わせた方法である。山中研究室より供与された201B7細胞に加え、患者皮膚細胞を採取し、皮膚細胞に山中4因子をレトロウイルスで導入することで樹立した患者の遺伝子異常を持ったiPS細胞でも、誘導を開始した。患者由来iPS細胞では、遺伝子導入部位などにより、その性質に株間のばらつきがある可能性があった。そこで樹立した患者由来細胞株50ラインのうちで、トランスジーン(4因子)の検定等の解析から、iPS細胞の性質を持つと判断された細胞株において、申請者の研究室で網膜細胞を誘導し、その性質を解析中である。分化誘導された細胞で、Pax6などの特徴的転写因子、ロドプシンなどの特異的マーカーを発現していることを確認している。また、網膜への分化誘導が可能で、研究に有用と判断された細胞株において、さらにiPS細胞の性質を確定するために、マウスへの移植を行い、テラトーマの作成による3胚葉への分化の可能性があることを実証した。
本研究で、患者遺伝子異常を持つiPS細胞由来の網膜細胞を培養可能になることは、その遺伝子異常による病態の解析に必須であり、重要なステップである。本細胞を用いた病態解明を、引き続き進める予定である。

Research Products

• [Journal Article] Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes. (2010)
  • Author(s): Sasaki M, Ozawa Y, Kurihara T, Kubota S, Yuki K, Noda K, Kobayashi S, Ishida S, Tsubota K.
  • Journal Title: Diabetologia. Volume: 53(5) Pages: 971-9
  • Peer Reviewed
• [Journal Article] von Hippel-Lindau protein regulates transition from the fetal to the adult circulatory system in retina. (2010)
  • Author(s): Kurihara T, Kubota Y, Ozawa Y, Takubo K, Noda K, Simon MC, Johnson RS, Suematsu M, Tsubota K, Ishida S, Goda N, Suda T, Okano H.
  • Journal Title: Development. Volume: 137(9) Pages: 1563-71
  • Peer Reviewed
• [Journal Article] Eicosapentaenoic acid suppresses ocular inflammation in endotoxin-induced uveitis. (2010)
  • Author(s): Suzuki M, Noda K, Kubota S, Hirasawa M, Ozawa Y, Tsubota K, Mizuki N, Ishida S.
  • Journal Title: Mol Vis. Volume: 17 Pages: 1382-8
  • Peer Reviewed
• [Journal Article] Retinal aging and sirtuins. (2010)
  • Author(s): Ozawa Y, Kubota S, Narimatsu T, Yuki K, Koto T, Sasaki M, Tsubota K.
  • Journal Title: Ophthalmic Res. Volume: 44(3) Pages: 199-203
  • Peer Reviewed
• [Presentation] Oxidative stress and diabetic retinopathy. (2010)
  • Author(s): Ozawa Y.
  • Organizer: The 24th Asia Pacific Academy of Ophthalmology Congress.
  • Place of Presentation: Beijing, China
  • Year and Date: 20100916-20100920
• [Presentation] Resveratrol prevents light-induced retinal degeneration via suppressing activator protein-1 activation. (2010)
  • Author(s): Kubota S, Kurihara T, Ebinuma M, Kubota M, Yuki K, Sasaki M, Noda K, Ozawa Y, Oike Y, Ishida S, Tsuboto K.
  • Organizer: Gordon Research Conference : Biology of Aging.
  • Place of Presentation: Les Diablerets, Switzerland
  • Year and Date: 20100822-20100827
• [Presentation] Spatial distribution of VEGF establishes proper retinal vascular patterning via VHL/HIF-1 pathway. (2010)
  • Author(s): Kurihara T, Kubota Y, Ozawa Y, Suda T, Okano H, Tsubota K.
  • Organizer: Gordon Research Conference : Biology of Aging.
  • Place of Presentation: Les Diablerets, Switzerland
  • Year and Date: 20100822-20100827
• [Presentation] Yellow intraocular lens implantation prevents light-induced retinal damage in mice. (2010)
  • Author(s): Ebinuma M, Kurihara T, Omoto M, Noda K, Kubota S, Ozawa Y, Shimmura S, Ishida S, Tsubota K.
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.
  • Place of Presentation: Fort Lauderdale, FL, USA
  • Year and Date: 20100502-20100506
• [Presentation] Localization of transcriptional factors associated with epithelial-mesenchymal transition in choroidal neovascularization. (2010)
  • Author(s): Hirasawa M, Noda K, Suzuki M, Ogawa Y, Ozawa Y, Tsubota K, Ishida S.
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.
  • Place of Presentation: Fort Lauderdale, FL, USA
  • Year and Date: 20100502-20100506
• [Presentation] Resveratrol suppresses ocular inflammation in the diabetic retina. (2010)
  • Author(s): Kubota S, Kurihara T, Noda K, Ozawa Y, Oike Y, Ishida S, Tsubota K.
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.
  • Place of Presentation: Fort Lauderdale, FL, USA
  • Year and Date: 20100502-20100506
• [Presentation] von Hippel-lindau tumor suppressor protein is required for transition from embryonic to adult circulatory system in retina. (2010)
  • Author(s): Kurihara T, Kubota Y, Ozawa Y, Noda K, Johnson RS, Goda N, Ishida S, Tsubota K, Suda T, Okano H.
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.
  • Place of Presentation: Fort Lauderdale, FL, USA
  • Year and Date: 20100502-20100506
• [Presentation] Neuroprotective effect of an antioxidant lutein in light-induced retinal degeneration. (2010)
  • Author(s): Sasaki M, Ozawa Y, Kurihara T, Kubota S, Yuki K, Noda K, Kobayashi S, Ishida S, Tsubota K.
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.
  • Place of Presentation: Fort Lauderdale, FL, USA
  • Year and Date: 20100502-20100506
• [Presentation] Purification of iPS cells derived from a retinitis pigmentosa patient from feeder cells. (2010)
  • Author(s): Yoshida T, Koizumi H, Yuki K, Tsubota K, Okano H, Ozawa Y.
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.
  • Place of Presentation: Fort Lauderdale, FL, USA
  • Year and Date: 20100502-20100506
• [Presentation] Superoxide dismutase 1 -/- mice as a model of normal-tension glaucoma. (2010)
  • Author(s): Yuki K, Yoshida T, Kurihara T, Kubota S, Sasaki M, Noda K, Ishida S, Ozawa Y, Tsubota K
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.
  • Place of Presentation: Fort Lauderdale, FL, USA
  • Year and Date: 20100502-20100506
• [Remarks]
  • URL: http://www.keio-eye.net/research/rcb.html