Investigation of the pathogenesis of proliferative vitreoretinal diseases and development of new drug therapy

• Project/Area Number: 19592026
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyushu University
• Principal Investigator: HATA Yasuaki Kyushu University, 大学院・医学研究院, 准教授 (90346776)
• Co-Investigator(Kenkyū-buntansha): ISHIBASHI Tatsuro 九州大学, 大学院・医学研究院, 教授 (30150428) ; GOTO Yoshinobu 国際医療福祉大学, 保険学部, 准教授 (30336028) ; SONODA Koh-hei 九州大学, 大学院・医学研究院, 講師 (10294943)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 糖尿病網膜症 / 増殖硝子体網膜症 / 形質転換増殖因子-β / ROCK / 硝子体細胞 / TGF-β / Rho / スタチン / 瘢痕収縮 / TGF-beta

Research Abstract

未だ有効な薬物療法が確立されていない増殖糖尿病網膜症や増殖性硝子体網膜症の病態に生理活性物質として形質転換増殖因子-・(TGF-・)、そのシグナル伝達分子としてRho-kinase(ROCK)が関与していることを明らかにし、ROCK 阻害薬を用いた新規の薬物療法の可能性を示した。

Research Products

• [Journal Article] Rho kinase inhibition by fasudil ameliorates diabeted-induced microvascular damage (2009)
  • Author(s): Arita R, Hata Y, Nakao S, Kita T, Miura M, Kawahara S, Zandi S, Almulki L, Tayyari F, Shimokawa H, Ali Hafezi-Moghadam, Ishibashi T
  • Journal Title: Diabetes 58 Pages: 215-226
• [Journal Article] Rho kinase inhibition by fasudil ameliorates diabeted-induced microvascular damage. (2009)
  • Author(s): Arita R, Hata Y, et al.
  • Journal Title: Diabetes 58 Pages: 215-226
  • Peer Reviewed
• [Journal Article] Antiangiogenic property of fasudil, a potent Rho-kinase inhibitor (2008)
  • Author(s): Hata Y, Miura M, Nakao S, Kawahara S, Kita T, Ishibashi T.
  • Journal Title: Jpn J Ophthalmol 52 Pages: 16-23
  • NAID: 10024153429
• [Journal Article] The internal limiting membrane peeling with Brilliant Blue G staining for retinal detachment due to macular hole in high myopia (2008)
  • Author(s): Mochizuki Y, Enaida H, Hisatomi T, Hata Y, Miura M, Arita R, Kawahara S, Kita T, Ueno A, Ishibashi T.
  • Journal Title: Br J Ophthalmol 92(7) Pages: 1009-1009
• [Journal Article] Posterior vitreous cortex characteristics of an eye with asteroid hyalosis (2008)
  • Author(s): Mochizuki Y, Hata Y, Hisatomi T, Kawahara S, Arita R, Enaida H, Ueno A, Ishibashi T.
  • Journal Title: Retinal Cases & Brief Reports 2(3) Pages: 184-186
• [Journal Article] VEGF expression by hyalocytes and its regulation by glucocorticoid (2008)
  • Author(s): Hata Y, Sassa Y, Kita T, Miura M, Kano K, Kawahara S, Arita R, Nakao S, Shih JL, Ishibashi T.
  • Journal Title: Br J Ophthalmol 92 Pages: 1540-1544
• [Journal Article] Potenti Inhibition of cicatricial contraction in proliferative vitreoretinal diseases by statins (2008)
  • Author(s): Kawahara S, Hata Y, Kita T, Arita R, Miura M, Nakao S, Mochizuki Y, Enaida H, Kagimoto T, Goto Y, Ali Hafezi-Moghadam, Ishibashi T
  • Journal Title: Diabetes 57 Pages: 2784-2793
• [Journal Article] Role of TGF-β in proliferative vitreoretinal diseases and ROCK as a therapeutic target (2008)
  • Author(s): Kita T, Hata Y, Arita R, Kawahara S, Miura M, Nakao S, Mochizuki Y, Enaida H, Goto Y, Shimokawa H, Ali Hafezi-Moghadam, Ishibashi T
  • Journal Title: Proc Natl Acad Sci USA 105 Pages: 17504-17509
• [Journal Article] Role of TGF-β in proliferative vitreoretinal diseases and ROCK as a therapeutic target. (2008)
  • Author(s): Kita T, Hata Y, et al.
  • Journal Title: Proc Natl Acad Sci USA. 105 Pages: 17504-17509
  • Peer Reviewed
• [Journal Article] Potenti Inhibition of cicatricial contraction in proliferative vitreo retinal diseases by statins. (2008)
  • Author(s): Kawahara S, Hata Y, et al.
  • Journal Title: Diabetes 57 Pages: 2784-2793
  • Peer Reviewed
• [Journal Article] Potent Inhibition of Cicatricial Contraction in Proliferative Vitreoretinal Diseases by Statins (2008)
  • Author(s): Kawahara S, Hata Y, et. al.
  • Journal Title: Diabetes (In press)
• [Journal Article] Antiangiogenic property of fasudil,a potent Rho-kinase inhbitor (2008)
  • Author(s): Hata Y, et. al.
  • Journal Title: Jpn J Ophthalmol 52 Pages: 16-23
• [Journal Article] Triamcinolone acetonide-assisted pars plana vitrectomy improves residual posterior vitreous hyaloid removal (2007)
  • Author(s): Matsumoto H, Yamanaka I, Hisatomi T, Enaida H, Ueno A, Hata Y, Sakamoto T, Ogino N, Ishibashi T
  • Journal Title: Ultrastructural analysis of the inner limiting membrane. Retina 27 Pages: 174-179
• [Journal Article] Reduced incidence of intraoperative complications in a multicenter controlled clinical trial of triamcinolone in vitrectomy (2007)
  • Author(s): Yamakiri K, Sakamoto T, Noda Y, Nakahara M, Ogino N, Kubota T, Yokoyama M, Furukawa M, Sonoda S, Yamada T, Doi N, Enaida H, Hata Y, Ishibashi T
  • Journal Title: Ophthalmology 114(2) Pages: 289-296
• [Journal Article] TGF-β2 and CTGF in proliferative vitreoretinal diseases (2007)
  • Author(s): Kita T, Hata Y, Kano K, Miura M, Nakao S, Noda Y, Shimokawa H, Ishibashi T
  • Journal Title: ~Possible involvement of hyalocytes and therapeutic potential of Rho kinase inhibitor~ Diabetes 56(1) Pages: 231-238
• [Journal Article] Preclinical investigation of fluorometholone acetate as a potential new adjuvant during vitreous surgery (2007)
  • Author(s): Hata Y, Enaida H, Sassa Y, Ueno A, Miura M, Hisatomi T, Goto Y, Ishibashi T
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 245 Pages: 1019-1025
• [Journal Article] Aqueous and vitreous penetration of levofloxacin after topical and/or oral administration (2007)
  • Author(s): Sakamoto H, Sakamoto M, Hata Y,Kubota T, Ishibashi T
  • Journal Title: Eur J Ophthaolmol 17 Pages: 372-376
• [Journal Article] Interleukin-18 regulates pathological intraocular neovascularization (2007)
  • Author(s): Qiao H, Sonoda K-H, Ikeda Y, Yoshimura T, Hijioka K, Jo Y-J, Sassa Y, Tsutsumi-Miyahara C, Hata Y, Akira S, Ishibashi T
  • Journal Title: J Leuk Biol 81(4) Pages: 1012-1021
• [Journal Article] Biocompatibility of Brilliant Blue G in a rat model of subretinal injection (2007)
  • Author(s): Ueno A, Hisatomi T, Enaida H, Kagimoto T, Mochizuki Y, Goto Y, Kubota T, Hata Y, Ishibashi T
  • Journal Title: Retina 27 Pages: 499-504
• [Journal Article] Functional characteristics of connective tissue growth factor on vitreoretinal cells (2007)
  • Author(s): Kita T, Hata Y, Miura M, Kawahara S, Nakao S, Ishibashi T.
  • Journal Title: Diabetes 56 Pages: 1421-1428
• [Journal Article] Long-term clinical outcomes and therapeutic benefits of triamcinolone-assisted pars plana vitrectomy for proliferative vitreoretinopathy (2007)
  • Author(s): Ueno A, Enaida H, Hata Y, Hisatomi T, Nakamura T, Mochizuki Y, Sakamoto T, Ishibashi T.
  • Journal Title: a case study. Eur J Ophthalmol 17 Pages: 392-398
• [Journal Article] Dexamethasone Inhibits IL-1β-Induced Corneal Neovascularization (2007)
  • Author(s): Nakao S, Hata Y, Miura M, Noda K, N.Kimura Y, Kawahara S, Kita T, Hisatomi T, Nakazawa T, Jin Y, Dana R, Kuwano M, Ono M, Ishibashi T, and H-Moghadam A.
  • Journal Title: Role of NF-κB-activated Stromal Cells in Inflammatory Angiogenesis. Am J Pathol 171(3) Pages: 1058-1065
• [Journal Article] Intracellular events in retinal glial cells exposed to ICG and BBG (2007)
  • Author(s): Kawahara S, Hata Y, Miura M, Kita T, Sengoku A, Nakao S, Mochizuki Y, Enaida H, Ueno A, H-Moghadam A, Ishibashi T.
  • Journal Title: Invest Ophthalmol Vis Sci 48 Pages: 4426-4432
• [Journal Article] Functional characteristics of connective tissue growth factoron vitreoretinal cells (2007)
  • Author(s): Kita T, Hata Y, et. al.
  • Journal Title: Diabetes 56 Pages: 1421-1428
• [Journal Article] Preclinical investigation of fluorometholone acetate as aopotential new adjuvant during vitreous surgery (2007)
  • Author(s): Hata Y, et. al.
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 245 Pages: 1019-1025
• [Journal Article] TGF-β2 and CTGF in proliferative vitreoretinal diseases 〜Possible involvement of hyalocytes and therapeutic potential of Rho kinase inhibitor (2007)
  • Author(s): Kita T, Hata Y, et. al.
  • Journal Title: Diabetes 56 Pages: 231-238
• [Presentation] 糖尿病硝子体網膜症の予防的治療戦略 (2008)
  • Author(s): 畑 快右
  • Organizer: 第112回日本眼科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-04-16
• [Presentation] Crucial Roles of TGF-beta2 in Proliferative Vitreoretinal Diseases and Rho-Kinase Pathway as a Therapeutic Target (2008)
  • Author(s): Kita T, Hata Y, Arita R, Kawahara S, Miura M, Nakao S, Mochizuki Y, Ueno A, Hafezi-Moghadam A, Ishibashi T
  • Organizer: The Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, Florida, USA
• [Presentation] Therapeutic potential of Rho-kinase inhibitors for proliferative vitreo-retinal diseases (2007)
  • Author(s): Hata Y.
  • Organizer: COE The 4^<th> international symposium
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2007-11-07
• [Presentation] Preclinical investigation of fluorometholone acetate as a potential new adjuvant during Vitreous surgery (2007)
  • Author(s): Hata Y, Enaida H, Sassa Y, Ueno A, Miura M, Hisatomi T, Goto Y, Ishibashi T.
  • Organizer: Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, Florida, USA
• [Presentation] Bullous retinal detachment after single photodynamic therapy (2007)
  • Author(s): Arita R, Hata Y, Noda Y, Ueno A, Enaida H, Mochizuki Y, Ishibashi T
  • Organizer: Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, Florida, USA
• [Presentation] Comprehensiveanalysis of cytokine/chemokine profile in vitreous fluid of diabetic retinopathy (2007)
  • Author(s): Sugahara M, Yoshimura T, Sonoda KH, Mochizuki Y, Enaida H, Oshima Y, Ueno A, Hata Y, Ishibashi T
  • Organizer: Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, Florida, USA
• [Presentation] Dexamethasone Inhibits IL-1β-Induced Corneal Neovascularization : Role of NF-κB-activated Stromal Cells in Inflammatory Angiogenesis (2007)
  • Author(s): Nakao S, Hata Y, Miura M, Noda K, Kimura YN, Kawahara S, Kita T, Hisatomi T, Nakazawa T, Jin Y, Dana R, Kuwano M, Ono M, Ishibashi T, andH-Moghadam A
  • Organizer: Gordon Research Conference (Angiogenesis)
  • Place of Presentation: Salve Regina University Newport, RI
• [Presentation] The internal limiting membrane peeling with adjust use of brilliant blue G staining for retinal detachment due to macular hole in high myopia (2007)
  • Author(s): Mochizuki Y, Enaid H, Hata Y, Arita R, Kawahara S, Miura M, Ueno A, Ishibashi T
  • Organizer: Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, Florida, USA
• [Book] 日本眼科学会雑誌113(3) (2009)
  • Author(s): 畑 快右
  • Publisher: 日本眼科学会
• [Patent(Industrial Property Rights)] スタチン系化合物を含有する眼内疾患の治療・予防薬 (2007)
  • Inventor(s): 畑快右
  • Industrial Property Rights Holder: 畑快右
  • Filing Date: 2007-10-15