The mechanism of photoreceptor cell differentiation to utilize in retinal regenerative therapy

• Project/Area Number: 19592038
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Keio University
• Principal Investigator: OZAWA Yoko Keio University, 医学部, 講師 (90265885)
• Co-Investigator(Kenkyū-buntansha): IMAI Takao 慶應義塾大学, 医学部, 助教 (10383712) ; KURIHARA Toshihide 慶應義塾大学, 医学部, 研究員(非常勤) (50365342)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 網膜 / 視機能 / 発生 / 再生 / 炎症 / サイトカイン / 分化 / シグナル伝達

Research Abstract

自然経過では再生しない網膜視細胞を分化誘導し、網膜機能を再生することは、現代の大きな課題の一つである。しかし、これまでの研究では、網膜細胞の中でも視細胞は誘導されにくいことが知られていた。一方、再生すべき網膜微小環境では通常とは異なった各種シグナルが活性化されている。その中で今回我々は、視細胞分化と、炎症刺激でも活性化されるNotchシグナルの関係を分子レベルで解析し、Numbが視細胞分化を許容し得ることを明らかにした。

Research Products

• [Journal Article] Musashi-1, an RNA-binding protein, is indispensable for survival of photoreceptors (2009)
  • Author(s): Suzuki K, Kaneko J, Yamano Y, Nakamura K, Inami W, Yoshikawa T, Ozawa Y, Shibata S, Matsuzaki O, Okano H, Chiba C
  • Journal Title: Exp Eye Res [Epub ahead of print] 88(3) Pages: 347-355
• [Journal Article] Neuroprotective Effect of an Antioxidant, Lutein, during Retinal Inflammation. (2009)
  • Author(s): Sasaki M, Ozawa Y, Kurihara T, et al
  • Journal Title: Invest Ophthalmol Vis Sci. 50(3) Pages: 1433-1439
  • Peer Reviewed
• [Journal Article] Equally contributed. Neuroprotective Effect of anAntioxidant, Lutein, during RetinalInflammation (2008)
  • Author(s): Sasaki M, Ozawa Y, Kurihara T, Noda K, Imamura Y, Kobayashi S, Ishida S, Tsubota K
  • Journal Title: Invest Ophthalmol Vis Sci 50(3) Pages: 1433-1439
• [Journal Article] (Pro)renin Receptor Promotes Choroidal Neovascularization by Activating Its Signal Transduction and Tissue Renin-Angiotensin System (2008)
  • Author(s): Satofuka S, Ichihara A, Nagai N, Noda K, Ozawa Y, Fukamizu A, Tsubota K, Itoh H, Oike Y, Ishida S
  • Journal Title: Am J Pathol Nov 13
• [Journal Article] Age-related macular degeneration (AMD) ; From pathogenesis and approved therapies to proposed treatments for prevention (2008)
  • Author(s): Ozawa Y, Ishida S, Tsubota K
  • Journal Title: Anti-Aging Medicine 5(7) Pages: 82-87
  • NAID: 130000125409
• [Journal Article] Roles of STAT3/SOCS3 pathway in regulating the visual function and ubiquitin-proteasome-dependent degradation of Rhodopsin during retinal inflammation (2008)
  • Author(s): Ozawa Y, Kurihara T, Nakao K, Shimazaki T, Shimmura S, Ishida S, Yoshimura A, Tsubota K, Okano H
  • Journal Title: J. Biol Chem 283(36) Pages: 24561-24570
• [Journal Article] Equally contributed. Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina (2008)
  • Author(s): Kurihara T, Ozawa Y, Nagai N, Shinoda K, Noda K, Imamura Y, Tsubota K, Okano H, Oike Y, Ishida S
  • Journal Title: Diabetes 57(8) Pages: 2191-2198
• [Journal Article] Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice (2008)
  • Author(s): Hashizume K, Hirasawa M, Imamura Y, Noda S, Shimizu T, Shinoda K, Kurihara T, Noda K, Ozawa Y, Ishida S, Miyake Y, Shirasawa T, Tsubota K
  • Journal Title: Am J Pathol 172(5) Pages: 1325-1331
• [Journal Article] Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin (2008)
  • Author(s): Izumi-Nagai K, Nagai N, Ohgami K, Satofuka S, Ozawa Y, Tsubota K, Ohno S, Oike Y, Ishida S
  • Journal Title: Invest Ophthalmol Vis Sci 49(4) Pages: 1679-1685
• [Journal Article] Structural analysis of Musashi-RNA complex on the basis of long-range structural information (2008)
  • Author(s): Ohyama T, Furukawa A, Mashima T, Sugiyama T, Ohgara S, Yamazaki T, Imai T, Okano H, Nagata T, Katahira M
  • Journal Title: Nucleic Acids Symp Ser (Oxf) 52 Pages: 193-194
• [Journal Article] Neural RNA-binding protein Musashil inhibits translation initiation by competing with eIF4G for PABP (2008)
  • Author(s): Kawahara H, Imai T, Imataka H, Tsujimoto M, Matsumoto K, Okano H
  • Journal Title: J Cell Biol 181(4) Pages: 639-653
• [Journal Article] Roles of STAT3/SOCS3 pathway in regulating the visual function and ubiquitin-proteasome-dependent degradation of Rhodopsin during retinal inflammation. (2008)
  • Author(s): Ozawa Y, Kurihara T, Nakao K, et al
  • Journal Title: J. Biol Chem. 283(36) Pages: 24561-24570
  • Peer Reviewed
• [Journal Article] Angiotensin II Type 1 Receptor Signaling Contributes to Synaptoptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina. (2008)
  • Author(s): Kurihara T, Ozawa Y, Nagai N, et al
  • Journal Title: Diabetes 57(8) Pages: 2191-2198
  • Peer Reviewed
• [Journal Article] Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin. (2008)
  • Author(s): Izumi-Nagai K, Nagai N, Ozawa Y, et al
  • Journal Title: Invest Ophthalmol Vis Sci. 49(4) Pages: 1679-1685
  • Peer Reviewed
• [Journal Article] Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice. (2008)
  • Author(s): Hashizume K, Ozawa Y, Tsubota K, et al
  • Journal Title: Am J Pathol. 172(5) Pages: 1325-1331
  • Peer Reviewed
• [Journal Article] Macular pigment lutein is antiinflammatory in preventing choroidal neovascularization (2007)
  • Author(s): Izumi-Nagai K, Nagai N, Ohgami K, Satofuka S, Ozawa Y, Tsubota K, Umezawa K, Ohno S, Oike Y, Ishida S
  • Journal Title: Arterioscler Thromb Vasc Biol 27(12) Pages: 2555-2562
• [Journal Article] Rhegmatogenous retinal detachment associated with primary congenital glaucoma (2007)
  • Author(s): Satofuka S, Imamura Y, Ishida S, Ozawa Y, Tsubota K, Inoue M
  • Journal Title: Int Ophthalmol 26
• [Journal Article] Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice (2007)
  • Author(s): Koto T, Nagai N, Mochimaru H, Kurihara T, Izumi-Nagai K, Satofuka S, Shinoda H, Noda K, Ozawa Y, Inoue M, Tsubota K, Oike Y, Ishida S
  • Journal Title: Invest Ophthalmol Vis Sci 48(9) Pages: 4328-4334
• [Journal Article] Patients' descriptions of visual sensations during pars plana vitrectomy under retrobulbar anesthesia (2007)
  • Author(s): Sugisaka E, Shinoda K, Ishida S, Imamura Y, Ozawa Y, Shinoda H, Suzuki K, Tsubota K, Inoue M
  • Journal Title: Am J Ophthalmol 144(2) Pages: 245-251
• [Journal Article] Interleukin-6 receptor-mediated activation of signal transducer and activator of transcription-3 (STAT3) promotes choroidal neovascularization (2007)
  • Author(s): Izumi-Nagai K, Nagai N, Ozawa Y, Mihara M, Ohsugi Y, Kurihara T, Koto T, Satofuka S, Inoue M, Tsubota K, Okano H, Oike Y, Ishida S
  • Journal Title: Am J Pathol 170(6) Pages: 2149-2158
• [Journal Article] Suppression of choroidal neovascularization by inhibiting angiotensin-converting enzyme : minimal role of bradykinin (2007)
  • Author(s): Nagai N, Oike Y, Izumi-Nagai K, Koto T, Satofuka S, Shinoda H, Noda K, Ozawa Y, Inoue M, Tsubota K, Ishida S
  • Journal Title: Invest Ophthalmol Vis Sci 48(5) Pages: 2321-2326
• [Journal Article] Interactions with RNA/DNA of proteins involved in the regulation of transcription, translation and telomere elongation (2007)
  • Author(s): Ohyama T, Furukawa A, Miyoshi T, Takada Y, Ohgara S, Hiratsuka K, Imai T, Okano H, Nakagama H, Nagata T, Katahira M
  • Journal Title: Nucleic Acids Symp Ser (Oxf) 51 Pages: 77-78
• [Journal Article] SOCS3 is required to temporally fine-tune photoreceptor cell differentiation (2007)
  • Author(s): Ozawa Y, Nakao K, Okano H, et. al.
  • Journal Title: Dev Biol. 303(2) Pages: 591-600
  • Peer Reviewed
• [Journal Article] Interleukin-6 receptor-mediated activation of signal transducer and activator oftranscription-3 (STAT3)promotes choroidal neovascularization (2007)
  • Author(s): Izumi-Nagai K, Nagai N, Ozawa Y, Ishida S., et. al.
  • Journal Title: Am J Pathol. 170(6) Pages: 2149-2158
  • Peer Reviewed
• [Journal Article] Macular pigment lutein is antiinflammatory in preventing choroidal neovascularization (2007)
  • Author(s): Nagai N, Izumi-Nagai K, Ozawa Y, Ishida S., et. al.
  • Journal Title: Arterioscler Thromb Vasc Biol. 27(12) Pages: 2555-2562
  • Peer Reviewed
• [Presentation] 網膜炎症による視機能障害に対するSOCS3の神経保護効果の解析SOCS3 is required to protect photoreceptor cell function during retinal inflammation (2008)
  • Author(s): Yoko Ozawa, Keiko Nakao, Toshihide Kurihara, Takuya Shimazaki, Shigeto Shimmura, Susumu Ishida, Akihiko Yoshimura, Kazuo Tsubota, Hideyuki Okano
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] 網膜炎症による視機能障害に対するSOCS3の神経保護効果の解析SOCS3 is required to protect photoreceptor cell function during retinal inflammation. (2008)
  • Author(s): Yoko Ozawa, et al
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] SOCS3 is required to protect photoreceptor cell function during retinal inflammation (2008)
  • Author(s): Yoko Ozawa, Keiko Nakao, Toshihide Kurihara, Takuya Shimazaki, Shigeto Shimmura, Susumu Ishida, Akihiko Yoshimura, Kazuo Tsubota, Hideyuki Okano
  • Organizer: 第31回日本神経科学会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-11
• [Presentation] SOCS3 is required to protect photoreceptor cell function during retinal inflammation. (2008)
  • Author(s): Yoko Ozawa, et al
  • Organizer: ARVO (The Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Ft. Lauderdale, Florida USA
  • Year and Date: 2008-05-02
• [Presentation] Neuroprotective roles of luteln in endotoxln-induced uveitis (2008)
  • Author(s): M, Sasaki, Y. Ozawa, T, Kurihara, et al
  • Organizer: ARVO (The Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Ft. Lauderdale, Florida USA
  • Year and Date: 2008-05-02
• [Presentation] SOCS3 is required to protect photoreceptor cell function during retinal inflammation (2008)
  • Author(s): Yoko Ozawa, Keiko Nakao, Toshihide Kurihara, Takuya Shimazaki, Shigeto Shimmura, Susumu Ishida, Akihiko Yoshimura, Kazuo Tsubota, Hideyuki Okano
  • Organizer: ARVO (The Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Ft. Lauderdale, Florida USA
  • Year and Date: 2008-04-27
• [Presentation] Angiotensin II type 1 receptor (AT1R)-mediated post-transcriptional reduction of synaptophysin in neuronal cells : a mechanism of neurodegeneration in the diabetic retina (2008)
  • Author(s): T. Kurihara, Y. Ozawa, N. Nagai, Y. Oike, H. Okano, K. Tsubota, and S. Ishida
  • Organizer: ARVO (The Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Ft. Lauderdale, Florida USA
  • Year and Date: 2008-04-27
• [Presentation] Neuroprotective roles of lutein in endotoxin-induced uveitis (2008)
  • Author(s): M. Sasaki, Y. Ozawa, T. Kurihara, S. Kobayashi, Y. Imamura, K. Noda, S. Ishida, K. Tsubota
  • Organizer: ARVO (The Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Ft. Lauderdale, Florida USA
  • Year and Date: 2008-04-27
• [Presentation] SOCS3 is required to temporally fine-tune photoreceptor cell differentiation (2007)
  • Author(s): Y Ozawa. K Nakao, T Shim azaki, S Shimmura, T Kurihara, S lshida, A Yoshimura, K Tsubota, H Okano.
  • Organizer: ARVO(The Association for Research in Vision and Onhthalmology)
  • Place of Presentation: Ft.Lauderdale, Florida USA
  • Year and Date: 2007-05-07
• [Presentation] 網膜視細胞の分化調節機構-SOCS3による正の制御-SOCS3は視細胞分化を開始させる (2007)
  • Author(s): 小澤洋子, 中尾啓子, 島崎琢也, 栗原俊英, 石田晋, 坪田一男, 岡野栄之
  • Organizer: 第28回炎症再生医学会総会
  • Place of Presentation: 東京
• [Presentation] SOCS3 is required to temporally fine-tune photoreceptor cell differentiation (2007)
  • Author(s): Yoko Ozawa, Keiko Nakao, Takuya Shimazaki, Shigeto Shimmura, Toshihide Kurihara, Susumu Ishida, Akihiko Yoshimura, Kazuo Tsubota, Hideyuki Okano
  • Organizer: ARVO (The Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Ft. Lauderdale, Florida USA
• [Presentation] Neuroprotective Effects of Angiotensin II type 1 (AT1-R) receptor blocker, Telmisartan in Early Diabetic retinopathy (2007)
  • Author(s): T. Kurihara, Y. Ozawa, N. Nagai, Y. Oike, H. Okano, K. Tsubota, and S. Ishida
  • Organizer: ARVO (The Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Ft. Lauderdale, Florida USA
• [Presentation] 網膜視細胞の分化調節機構-SOCS3による正の制御-SOCS3は視細胞分化を開始させる (2007)
  • Author(s): 小澤洋子, 中尾啓子, 島崎琢也, 栗原俊英, 石田晋, 坪田一男, 岡野栄之
  • Organizer: 第111回日本眼科学会総会
  • Place of Presentation: 大阪
• [Presentation] 眼炎症による網膜機能障害に対するアンジオテンシンII1型受容体阻害剤の効果 (2007)
  • Author(s): 栗原俊英、小沢洋子、永井紀博、篠田啓、井上真、尾池雄一、坪田一男、石田晋、岡野栄之
  • Organizer: 第111回日本眼科学会総会
  • Place of Presentation: 第111回日本眼科学会総会