Comprehensive and prompt basic science study for protecting retinal ganglion cell by combined system of cultured cell and individual animals and application for clinical approach

培养细胞与动物个体联合系统保护视网膜神经节细胞的全面、及时的基础科学研究及临床应用

• 批准号: 17591827
• 负责人: KASHIWAGI Kenji
• 金额: $ 2.24万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591827/
• 关键词: Retinal ganglion cell; Glaucoma; Animal disease model; culture model; transgenic model; 培養実験; 個体実験; 遺伝子改変動物; 網膜グリア細胞; 動物実験モデル; 神経細胞培養; グルタミン酸; 一酸化窒素

Ocular disease targeting retinal ganglion cell (RGC) loss, such as glaucoma that is secondary cause of acquired blindness in the world, may cause severe and irreversible visual dysfunction. Many kinds of treatment including clinical applied for other diseases are subject to be candidated treatment for this insult. In this particular investigation., we aimed to investigate the effectiveness of either candidated or unknown factors for rescuing RGC loss using prompt and accurate evaluation system for pursuing new clinical treatment. In results, we success to establish new evaluation system for RGC damage, and we investigate several new potential neuron-protective drugs such as latanoprost and iganijipine. We also revealed new aspects regarding mechanism of damage of retinal neuron such as regulating kinase 1 that plays a important role in apoptosis of RGC and success to develop new approach for neuron-protection. We also investigated single nucleotide polymorphisms in glaucoma in genes of OPA-1, apolipoprotein E, and Methylenetetrahydrofolate reductase gene. Furthermore, at present, we are working on revising new in vivo and in vitro disease models, preparing several types of transgenic animals with new evaluation system for them, and developing new animal disease models using primate for investigating RGC disturbance for conducting good platform of translational research system. Those of them are expected to contribute investigation for new aspects of disturbance mechanism of RGC and development of new therapy.

以视网膜神经节细胞(RGC)丢失为目标的眼病，如青光眼，是世界上继发性失明的第二原因，可能会导致严重的和不可逆转的视觉功能障碍。对于这种侮辱，包括临床上应用于其他疾病的多种治疗方法都是候选治疗。在这项特别的调查中，我们的目的是利用及时和准确的评估系统来研究候选因素和未知因素在挽救RGC损失方面的有效性，以寻求新的临床治疗方法。结果，我们成功地建立了RGC损伤的新的评估体系，并研究了拉坦前列素和伊加尼吉平等几种潜在的神经元保护药物。我们还揭示了视网膜神经元损伤机制的新方面，如调节在RGC细胞凋亡中起重要作用的激酶1，并成功地开发了神经元保护的新途径。我们还研究了OPA-1、载脂蛋白E和亚甲基四氢叶酸还原酶基因在青光眼中的单核苷酸多态性。此外，目前，我们正在修订新的体内和体外疾病模型，为它们准备几种类型的转基因动物和新的评估系统，并利用灵长类动物开发新的动物疾病模型来研究RGC干扰，为翻译研究系统提供良好的平台。这些研究成果可望为研究RGC的干扰机制和开发新的治疗方法做出新贡献。

项目成果

The effect of unoprostone isopropyl on Ca2+ release - Activated Ca2+ currents in cultured monkey trabecular meshwork cells and ciliary muscle cells

乌诺前列酮异丙酯对 Ca2 释放的影响 - 培养猴小梁网细胞和睫状肌细胞中激活的 Ca2 电流

• 发表时间: 2006
• 期刊: Journal of ocular pharmacology and therapeutics 22・4
• 作者: Shino Y;Mun H-S;He N;Nakazaki Y;Fang H;Furuya M;Aosai F;Yano A.;Munakata S;Shiono Y;矢野明彦;矢野明彦;Aosai F;Mun HS;矢野 明彦;矢野 明彦;Aosai F;Mun HS;Norose K;Naoi K;Kobayashi M;Aosai F;F.Mabuchi;F.Mabuchi et al.;F.Mabuchi;M.Shimura
• 通讯作者: M.Shimura

Methylenetetrahydrofolate reductase gene polymorphisms c.677C/T and c.1298AJC are not associated with open angle glaucoma

亚甲基四氢叶酸还原酶基因多态性 c.677C/T 和 c.1298AJC 与开角型青光眼无关

• 发表时间: 2006
• 期刊: Molecular Vision 7(12)
• 作者: Shino Y;Mun H-S;He N;Nakazaki Y;Fang H;Furuya M;Aosai F;Yano A.;Munakata S;Shiono Y;矢野明彦;矢野明彦;Aosai F;Mun HS;矢野 明彦;矢野 明彦;Aosai F;Mun HS;Norose K;Naoi K;Kobayashi M;Aosai F;F.Mabuchi;F.Mabuchi et al.;F.Mabuchi;M.Shimura;Aosai F;H.Kudo;Norose K;C.Harada;F.Mabuchi
• 通讯作者: F.Mabuchi

Role of apoptosis signal-regulating kinase 1 in stress-induced neural cell apoptosis in vivo

• DOI: 10.2353/ajpath.2006.050765
• 发表时间: 2006-01-01
• 期刊: AMERICAN JOURNAL OF PATHOLOGY
• 影响因子: 6
• 作者: Harada, C;Nakamura, K;Harada, T
• 通讯作者: Harada, T

Neuroprotective effect of latanoprost on rat retinal ganglion cells

• DOI: 10.1007/s00417-005-0215-0
• 发表时间: 2006-01
• 期刊: Graefe's Archive for Clinical and Experimental Ophthalmology
• 作者: H. Kudo;T. Nakazawa;M. Shimura;Hidetoshi Takahashi;N. Fuse;K. Kashiwagi;M. Tamai

Ocular distribution after topical instillation and potential neuroprotective effect after intravitreal injection of the calcium channel blocker iganipidine

局部滴注后的眼部分布以及玻璃体内注射钙通道阻滞剂伊加尼匹定后的潜在神经保护作用

• 发表时间: 2005
• 期刊: Current Eye Research 30・4
• 作者: Harada C;Nakamura K;Kashiwagi K;Yoshida K;Harada T;et al.;F.Mabuchi;M.Ohashi
• 通讯作者: M.Ohashi