The development and clinical application of molecular-based new medical treatments for glaucoma
| Project/Area Number |
16390500
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Kumamoto University |
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Principal Investigator |
TANIHARA Hidenobu Kumamoto University, Graduate School of Medical Sciences, Professor, 大学院・医学薬学研究部, 教授 (60217148)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUSHIMA Mikiko Kumamoto University, Hospital, Associate Professor, 医学部附属病院, 講師 (10284770)
KOGA Takahisa Kumamoto University, Hospital, Associate Professor, 医学部附属病院, 講師 (70372787)
KOSHIYAMA Yasuo Kumamoto University, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学薬学研究部, 助手 (40372784)
平田 憲 熊本大学, 医学部附属病院, 講師 (60295144)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2005: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2004: ¥9,700,000 (Direct Cost: ¥9,700,000)
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| Keywords | ROCK / Rho / Glaucoma / Amyloidosis / Neuroprotection / Transthyretin / ROCK阻害薬 / ヒト培養線維柱帯細胞 / DNAマイクロアレイ / プロテオミクス |
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| Research Abstract |
We investigated molecular mechanisms of intraocular pressure elevation and optic nerve damage in glaucoma to develop new medical treatment for glaucoma. We showed the clinical results about surgical reconstruction for aqueous outflow to investigate aqueous outflow resistance (Arch Ophthalmol 2004). Then, we examined genetic analyses of glaucoma to identify the relationship between the genetics and the aqueous outflow resistance (Exp Cell Res 2004 ; IOVS 2004 ; J Glaucoma 2004 ; Mol Vis 2005). In addition, we elucidated the molecular mechanism of amyloid-induced secondary glaucoma, which is derived from a single gene mutation. We reported the localization of mutant transthyretin in ocular tissues, the difficulties in clinical treatments for the ocular complications and the possibility of the gene therapy (Transplantation 2004 ; Gene Therapy 2004 ; Amyloid 2004 ; Exp Eye Res 2005 ; Ophthalmology 2005). Moreover, we investigated the pharmacologic effect of ROCK inhibitor, which reduces the aqueous outflow resistance, for trabecular meshwork cells (Exp Eye Res 2006). On the other hand, we showed the pathological significance of the interaction between leukocytes and endothelium in eye diseases, and showed that the inhibition of the interaction induces the neuroprotective effect in retinal tissues (IOVS 2004 ; Arch Ophthalmol 2004 ; Pro Natl Acad Sci USA, 2003). We also showed that the eye in pathological conditions expresses bioactive factors, also resulting in neuroprotective effects (NeuroReport 2004), and that the stress response in endoplasmic reticula plays an important role in neuroprotection (J Neurochem 2006).
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Report
(3 results)
Research Products
(59 results)
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[Journal Article] Expression of a chondroitin sulfate proteoglycan, PG-M/versican, during development of rat cornea.2005
Author(s)
Koga T, Inatani M, Hirata A, Inomata Y, Zako M, Kimata K, Oohira A, Gotoh T, Mori M, Tanihara H.
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Journal Title
Current Eye Rsearch 30
Pages: 455-463
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Lactoferrin Glu561Asp Facilitates Amyloid Formation in the Cornea.2005
Author(s)
Araki-Sasaki K, Ando Y, Nakamura M, Kitagawa K, Ikemizu S, Kawaji T, Yamashita T, Ueda M, Hirano K, Yamada M, Matsumoto K, Kinoshita S, Tanihara H.
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Journal Title
British Journal of Ophthalmology 89
Pages: 684-688
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association between glaucoma and gene polymorphism of endothelin type A receptor.2005
Author(s)
Ishikawa K, Funayama T, Ohtake.Y, Kimura I, Ideta H, Nakamoto K, Yasuda N, Fukuchi T, Fujimaki T, Murakami A, Asaoka R, Hotta Y, Kanamoto T, Tanihara H, Miyaki K, Mashima Y.
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Journal Title
Molecular Vision. 11
Pages: 431-437
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association between glaucoma and gene polymorphism of endothelin type A receptor.2005
Author(s)
Ishikawa K, Funayama T, Ohtake Y, Kimura I, Ideta H, Nakamoto K, Yasuda N, Fukuchi T, Fujimaki T, Murakami A, Asaoka R, Hotta Y, Kanamoto T, Tanihara H, Miyaki K, Mashima Y.
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Journal Title
Molecular Vision 11
Pages: 431-437
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[Journal Article] Lactoferrin Glu561Asp Facilitates Amyloid Formation in the cornea.2005
Author(s)
Araki-Sasaki K, Ando Y, Nakamura M, Kitagawa K, Ikemizu S, Kawaji T, Yamashita T, Ueda M, Hirano K, Yamada M, Matsumoto K, Kinoshita S, Tanihara H.
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Journal Title
British Journal of Ophthalmology 89
Pages: 684-688
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[Journal Article] A different amyloid formation mechanism. De novo oculoleptomeningeal amyloid deposits after liver transplantation.2004
Author(s)
Ando Y, Terazaki H, Nakamura M, Ando E, Haraoka K, Yamashita T, Ueda U, Okabe H, Sasaki Y, Tanihara H, Uchino M, Inomata Y.
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Journal Title
Transplantation 77
Pages: 345-349
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Targeted conversion of the tansthyretin gene in vitro and in vivo.2004
Author(s)
Nakamura M, Ando Y, Nagahara S, Sano A, Ochiya T, Maeda S, Kawaji T, Ogawa M, Hirata A, Terazaki H, Haraoka K, Tanihara H, Uchino M, Yamamura K.
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Journal Title
Gene Therapy 11
Pages: 838-846
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Platelets adhering to the vascular wall mediate postischemic leukocyte-endothelial cell interactions in retinal microcirculation.2004
Author(s)
Nishijima K, Kiryu J, Tsujikawa A, Miyamoto K, Honjo M, Tanihara H, Nonaka A, Yamashito K, Katsuta H, Miyahara S, Honda Y, Ogura Y.
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Journal Title
Investigative Ophthalmology & Visual Science 45
Pages: 977-984
Description
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[Journal Article] Variants in optineurin gene and their association with tumor necrosis factor-α polymorphisms in Japanese patients with glaucoma.2004
Author(s)
Funayama T, Ishikawa K, Ohtake Y, Tanino T, Kurosaka D, Kimura I, Suzuki K, Ideta H, Nakamoto K, Yasuda N, Fujimaki T, Murakami A, Asaoka R, Hotta Y, Tanihara H, Kanamoto T, Mishima H, Fukuchi T, Abe H, Iwata T, Shimada N, Kudoh J, Shimizu N, Mashima.Y.
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Journal Title
Investigative Ophthalmology & Visual Science 45
Pages: 4359-4367
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel MYOC Gene Mutation, Phe369Leu, in Japanese Patients with Primary Open-Angle Glaucoma Detected by Denaturing High-Performance Liquid Chromatography.2004
Author(s)
Ishikawa K, Funayama T, Ohtake Y, Tanino T, Kurosaka D, Suzuki K, Ideta H, Fujimaki T, Tanihara H, Asaoka R, Naoi N, Yasuda N, Iwata T, Mashima Y.
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Journal Title
Journal of Glaucoma 13
Pages: 466-471
Description
「研究成果報告書概要(欧文)」より
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