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The investigation for molecular mechanisms of aqueous humor outflow and the creation of new treatments for intraocular pressure elevation in glaucomatous eyes

青光眼眼房水流出的分子机制研究及眼压升高新疗法的开发

基本信息

批准号：
18390470
负责人：
TANIHARA Hidenobu
金额：
$ 10.59万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

The investigation for molecular mechanisms of aqueous humor outflow and the creation of new treatments for intraocular pressure elevation in glaucomatous eyesThe pathogenesis of primary open-angle glaucoma is derived from the unique optic neuropathy induced by intraocular pressure elevation. To treat the abnormal intraocular pressure elevation, we investigated for the resistance of aqueous humor outflow, a critical factor for intraocular pressure elevation. We examined pharmacological effects of ROCK inhibitors, which reduce aqueous humor resistance. Experiments using cultivated trabecular meshwork cells showed that ROCK inhibitor induces enhanced cell adhesion, relaxed cytoskeleton and changed structure of extracellular matrices. Moreover, our clinical trial for healthy volunteers showed that ROCK inhibitor dramatically reduces intraocular pressure in human eyes without serious side effects. The experiment using rabbit eyes showed that ROCK inhibitor keeps intraocular pressure lowering after the filtering surgery, a major glaucoma surgical procedure. Thus, we introduced ROCK inhibitors as new anti-glaucomatous drug, and inspired a new strategy for lowering intraocular pressure through physiological aqueous humor pathway. In addition, we examined the pathogenesis of secondary glaucoma, which is also induced by increased resistance of aqueous humor outflow. Triamcinolone acetonide, a popular corticosteroid drug, highly induces steroid-induced glaucoma. We reported the risk factors for steroid-induced glaucoma are the patients with young age, high baseline intraocular pressure, intravitreal injection of triamcinolone acetonide and high dose injection of triamcinolone acetonide. Last, we reported the complications after the surgery for a secondary glaucoma associated with familial amyloidosis, a hereditary disease exhibiting a high prevalence in Kumamoto, Japan.

原发性开角型青光眼的发病机制是由眼压升高引起的独特的视神经病变引起的。为了治疗异常眼压升高，我们研究了眼内压升高的关键因素--房水流出阻力。我们研究了ROCK抑制剂的药理学作用，其降低了房水阻力。使用培养的小梁网细胞的实验表明，ROCK抑制剂诱导增强的细胞粘附，松弛的细胞骨架和改变的细胞外基质的结构。此外，我们对健康志愿者的临床试验表明，ROCK抑制剂可显著降低人眼的眼内压，且无严重副作用。使用兔眼的实验表明，ROCK抑制剂在滤过手术（一种主要的青光眼手术程序）后保持眼内压降低。因此，我们引入了ROCK抑制剂作为新的抗青光眼药物，并启发了通过生理性房水途径降低眼内压的新策略。此外，我们研究了继发性青光眼的发病机制，这也是由增加阻力的房水流出。曲安奈德，一种常用的皮质类固醇药物，高度诱导类固醇诱导性青光眼。我们报告了激素性青光眼的危险因素是年轻患者、高基线眼压、玻璃体腔内注射曲安奈德和大剂量注射曲安奈德。最后，我们报告了与家族性淀粉样变性相关的继发性青光眼手术后的并发症，这是一种在日本熊本发病率很高的遗传性疾病。