Vascular effect of various antiglaucoma agent on ciliary artery smooth muscle cells.

各种抗青光眼药物对睫状动脉平滑肌细胞的血管作用。

• 批准号: 15591872
• 负责人: YOSHITOMI Takeshi
• 金额: $ 2.24万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591872/
• 关键词: glaucoma; antiglaucoma drug; Ocular circulation; vascular smooth muscle; contraction; intracellular calcium

Though it is generally accepted that decreasing intraocular pressure (IOP) is important to treat normal tension glaucoma (NTG), increasing ocular vascular perfusion is also considered to be important. The purpose of this study is to clarify the vasodilatory mechanism of various compound used for treatment of glaucoma, pharmacologically. We have investigated the effect of beta antagonists or prostaglandin related compounds on isolated rabbit and rat ciliary artery in vitro. These compound were reported to have effect on ocular circulation in addition to decrease IOP. Betaxolol dose-dependently relax rabbit ciliaryn artery by action similar to Ca antagonists. NIpradilol, another be-ta antagonist used for treatment of glaucoma, also relax rabbit ciliary artery as NO-donor. Levobumolol also relax this muscle by changing intracellular calcium sensitivity. All these be-ta antagonists relax rabbit ciliary artery by different mechanisms all which are not be-ta receptor antagonistic action. Unoprostone, a prostaglandin related compound also used for treatment of glaucoma, relax this muscle. The mechanism of muscle relaxation by unoprostone may be mediated by inhibition of Ca^<2+> entry, possibly through capacitative Ca^<2+> channels. Latanoprost, another prostaglandin related compound and stronger capability of reducing IOP also relax rabbit ciliary artery but the action is weaker than unoprostone. These results indicate that many antiglacoma agents relax vascular smooth muscle by various mechanisms which is different from the mechanisms of reducing IOP. These findings may provide useful information for developing new drugs for improving ocular circula

虽然人们普遍认为降低眼内压（IOP）对治疗正常眼压性青光眼（NTG）很重要，但增加眼血管灌注也被认为很重要。本研究的目的是阐明用于治疗青光眼、青光眼的各种化合物的扩血管机制。我们研究了β受体拮抗剂或前列腺素相关化合物对离体兔和大鼠睫状动脉的作用。据报道，这些化合物除了降低IOP外，还对眼循环有影响。倍他洛尔通过与Ca拮抗剂类似的作用剂量依赖性地舒张兔睫状动脉。另一种用于治疗青光眼的β-受体拮抗剂尼普拉地洛（Nipradilol）也可作为NO供体舒张兔睫状动脉。左丁洛尔还通过改变细胞内钙敏感性来放松肌肉。这些β受体拮抗剂均通过不同的机制舒张兔睫状动脉，但均不是β受体拮抗作用。乌诺前列酮，一种前列腺素相关化合物，也用于治疗青光眼，放松这块肌肉。乌诺前列酮的肌肉松弛机制可能是通过抑制Ca^2+内流介导的，可能是通过容量性Ca^2+通道。拉坦前列素是另一种前列腺素相关化合物，具有更强的降低IOP的能力，也舒张兔睫状动脉，但作用弱于乌诺前列酮。这些结果表明，许多抗青光眼药物通过多种机制松弛血管平滑肌，这与降低IOP的机制不同。这些发现为开发改善眼循环的新药提供了有用的信息。

项目成果

Ishikawa H, Uga S, Mashimo K, Yoshitomi T, Kusanagi M: "Pharmacological vascular reactivity in isolated hypercholesterolemic rabbit ciliary artery"Exp Eye Res. 78. 805-813 (2004)

Ishikawa H、Uga S、Mashimo K、Yoshitomi T、Kusanagi M：“离体高胆固醇血症兔睫状动脉的药理学血管反应性”Exp Eye Res。

Yoshitomi T, Yamaji K, Ishikawa H, Ohnishi Y: "Vasodilatory Mechanism of Unoprostone Isopropyl on Isolated Rabbit Ciliary Artery"Curr Eye res. 28. 167-174 (2004)

Yoshitomi T、Yamaji K、Ishikawa H、Ohnishi Y：“乌诺前列酮异丙酯对离体兔睫状动脉的血管舒张机制”Curr Eye res。

視神経の加齢変化

视神经的老化变化

• 发表时间: 2005
• 期刊: 眼科 47
• 作者: Kadonosono K;Yabuki K;Nishide T;Nomura E;Uchio E;Yamakawa T.;吉冨 健志
• 通讯作者: 吉冨 健志

緑内障大規模スタディの結果-EBMに向けて-

一项大规模青光眼研究的结果 - 迈向 EBM -

• 发表时间: 2004
• 期刊: 臨床眼科 58
• 作者: Saika S;Muragaki Y;Okada Y;Miyamoto T;Ohnishi Y;Ooshima A;Kao WW-Y.;Kadonosono K.;吉冨健志
• 通讯作者: 吉冨健志

原発開放隅角緑内障の点眼治療

滴眼液治疗原发性开角型青光眼

• 发表时间: 2005
• 期刊: 日本の眼科 76
• 作者: Saika S;Ikeda K;Yamanaka O;Flanders KC;Nakajima Y;Miyamoto T;Ohnishi Y;Kao WW-Y;Muragaki Y;Ooshima A.;吉冨 健志
• 通讯作者: 吉冨 健志