Development of new treatment modality for diabetic macular edema using knockout mice that show prominent retinal edema.

• Project/Area Number: 20390447
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Shinshu University
• Principal Investigator: MURATA Toshinori 信州大学, 医学部, 教授 (50253406)
• Co-Investigator(Kenkyū-buntansha): SHINDO Takayuki 信州大学, 医学系研究科, 教授 (90345215) ; ISHIBASHI Tatsuro 九州大学, 医学系研究科, 教授 (30150428)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000); Fiscal Year 2010: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2009: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2008: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 眼細胞生物学糖尿病黄斑浮腫治療 / 糖尿病黄斑浮腫 / アドレノメデュリン / ノックアウトマウス / RAMP-2 / 糖尿病網膜症 / 糖尿病 / タイトジャンクション / 基底膜 / 黄斑浮腫

Research Abstract

Homozygote RAMP-2 knockout(KO) mice are fatal before delivery, but heterozygote RAMP-2 KO mice show largely normal development except for systemic edema. We found these mice have marked retinal edema. Diabetic retinal edema is a leading cause of legal blindness. There has been no animal model for retinal edema.(RAMP)-2 knockout mice are new and the only existing animal model of retinal edema. Using this model, we reported that insufficient formation of tight junction and disruption of Bruch' s membrane are potential causes of breakdown of blood-retinal barrier.

Research Products

• [Journal Article] 糖尿病網膜症の発症と進展特集 糖尿病の病態を「見える化」してみる-どこまでわかりやすくできるか (2010)
  • Author(s): 村田敏規
  • Journal Title: Japanese Journal of Diabetes Master Clinician 8
• [Journal Article] Cardiac fibroblasts are essential for the adaptive response of the murine heart to pressure overload. (2010)
  • Author(s): Takeda N, Shindo T, Nagai R
  • Journal Title: 120 Pages: 254-265
• [Journal Article] Prevalence and systemic risk factors for retinal vein occlusion in a general Japanese population : the Hisayama Study (2010)
  • Author(s): Yasuda M,Ishibashi T
  • Journal Title: 51 Pages: 3205-3209
• [Journal Article] 糖尿病網膜症の発症と進展特集糖尿病の病態を見えるしてみる・どこまでわかりやすくできるか (2010)
  • Author(s): 村田敏規
  • Journal Title: Japanese Journal of Diabetes Master Clinician Volume: 8 Pages: 37-40
• [Journal Article] Cardiac fibroblasts are essential for the adaptive response of the murine heart to pressure overload (2010)
  • Author(s): Takeda N, Shindo T. Nagai R(12人中7番目)
  • Journal Title: J Clin Invest Volume: 120 Pages: 254-265
  • Peer Reviewed
• [Journal Article] Prevalence and systemic risk factors for retinal vein occlusion in a general Japanese population: the Hisayama Study (2010)
  • Author(s): Yasuda M, Ishibashi T(8人中8番目)
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 51 Pages: 3205-3209
  • Peer Reviewed
• [Journal Article] 糖尿病網膜症の発症と進展 特集 糖尿病の病態を「見える化」してみる-どこまでわかりやすくできるか (2010)
  • Author(s): 村田敏規
  • Journal Title: 糖尿病診療マスター 8 Pages: 37-40
• [Journal Article] Histopathological study of angle closure glaucoma secondary to retinopathy of prematurity (2009)
  • Author(s): Yanagidaira T, Miyahara T, Tokushima T, Yoshida A, Murata T
  • Journal Title: Jpn J Ophthalmol Volume: 53 Pages: 267-287
  • NAID: 10025150232
  • Peer Reviewed
• [Journal Article] Acute Toxicity Study of a Simian Immunodeficiency Virus-Based Lentiviral Vector for Retinal Gene Transfer in Nonhuman Primates (2009)
  • Author(s): Ikeda Y, Murata T, Ishibashi T
  • Journal Title: Hum Gene Ther Volume: 20(9) Pages: 943-954
  • Peer Reviewed
• [Journal Article] Stable Retinal Gene Expression in Nonhuman Primates via Subretinal Injection of SIVagm-based Lentiviral Vectors (2009)
  • Author(s): Ikeda Y, Murata T, Tabata T, Ueda Y, Ono F, Suzuki T, Ageyama N, Terao K, Hasegawa M, Sueishi K, Ishibashi T
  • Journal Title: Hum Gene Ther Volume: 20(6) Pages: 573-579
  • Peer Reviewed
• [Journal Article] Stable Retinal Gene Expression in Nonhuman Primates via Subretinal Injection of SIVagm-based Lentiviral Vectors Hum Gene Ther (2009)
  • Author(s): Ikeda Y, Murata T, Ishibashi T
  • Journal Title: 20 Pages: 943-954
• [Journal Article] Stable Retinal Gene Expression in Nonhuman Primates via Subretinal Injection of STVagm-based Lentiviral Vectors. (2009)
  • Author(s): Ikeda Y
  • Journal Title: Hum Gene Ther 6 Pages: 573-579
  • Peer Reviewed
• [Journal Article] Acute Toxicity Study of a Simian Immunodeficiency Virus-Based Lentiviral Vector for Retinal Gene Transfer in Nonhuman Primates. (2009)
  • Author(s): Ikeda Y
  • Journal Title: Hum Gene Ther 9 Pages: 943-954
  • Peer Reviewed
• [Journal Article] Stable Retinal Gene Expression in Nonhuman Primates via Subretinal Injection of SIVagm-based Lentiviral Vectors (2009)
  • Author(s): Ikeda Y
  • Journal Title: Hum Gene Ther. (in press)
  • Peer Reviewed
• [Journal Article] GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity (2008)
  • Author(s): Ichikawa-Shindo Y, Murata T, Kangawa K, Nagai R, Shindo T
  • Journal Title: J Clin Invest Volume: 118(1) Pages: 29-39
  • Peer Reviewed
• [Journal Article] Glutaraldehyde is an effective cross-linker for production of antibodies against advanced glycation end-products. (2008)
  • Author(s): Mera K, Murata T, Maruyama T, Baynes JW, Otagiri M, Nagai R
  • Journal Title: J Immunol Methods Volume: 334(1-2) Pages: 82-90
  • Peer Reviewed
• [Journal Article] Glutaraldehyde is an effective cross-linker for production of antibodies against advanced glycation end-products. (2008)
  • Author(s): Mera K, Murata T
  • Journal Title: J Immunol Methods 334 Pages: 82-90
• [Journal Article] GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity. (2008)
  • Author(s): Ichikawa-Shindo Y, Shindo T
  • Journal Title: 118 Pages: 29-39
• [Journal Article] GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity (2008)
  • Author(s): Yuka Ichikawa-Shindo
  • Journal Title: J Clin Invest 118 Pages: 29-39
  • Peer Reviewed
• [Journal Article] Glutaraldehyde is an effective cross-linker for production of antibodies against advanced glycation end-products. (2008)
  • Author(s): Mera K
  • Journal Title: J Immunol Methods 334 Pages: 82-90
  • Peer Reviewed
• [Presentation] 糖尿病網膜症合併血糖管理不良患者の血糖コントロール:緩徐に行うべきか否か? (2010)
  • Author(s): 村田敏規
  • Organizer: 第53回日本糖尿病学会年次学術集会Debate Session 4
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-28
• [Presentation] Histopahtological aspects of vitrectomy for diabetic retinopathy Sept 18 (2010)
  • Author(s): Murata T
  • Organizer: The 25^<th> APAO congress A joint meeting of APAO/AAO
  • Place of Presentation: Beijing China
• [Presentation] Converting to a 20G-vitrectomy from a small-incision vitrectomy for intractable cases (2010)
  • Author(s): Murata T
  • Organizer: The third joint meeting of China Korea Japan Ophthalmologists
  • Place of Presentation: Beijing China
• [Presentation] 糖尿病網膜症診療 (2009)
  • Author(s): 村田敏規
  • Organizer: 香川大学眼科研究会
  • Place of Presentation: 高松市
  • Year and Date: 2009-11-28
• [Presentation] 糖尿病網膜症の診療 (2009)
  • Author(s): 村田敏規
  • Organizer: 第11回教育フォーラム
  • Place of Presentation: 福岡市
  • Year and Date: 2009-10-31
• [Presentation] 糖尿病網膜症合併血糖管理不良患者の血糖コントロール:緩徐に行うべきか否か? (2009)
  • Author(s): 村田敏規
  • Organizer: 第53回日本糖尿病学会年次学術集会 Debate Session 4
  • Place of Presentation: 岡山
  • Year and Date: 2009-05-28
• [Presentation] Resolution of retinoschisis after vitrectomy in X-linked retinoschisis (2008)
  • Author(s): Murata T
  • Organizer: The third Congress of the Asian Pacific VitreoRetinal Society(APVRS2008)
  • Place of Presentation: Busan Korea
  • Year and Date: 2008-12-06
• [Presentation] The incidence of choroidal nevi in Japan (2008)
  • Author(s): Murata T
  • Organizer: Pathology Symposium World ophthalmology congress
  • Place of Presentation: Hong Kong
  • Year and Date: 2008-07-02