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

青光眼房水流出的分子机制研究及治疗青光眼眼内压升高的新方法原发性开角型青光眼的发病机制源于眼压升高引起的独特的视神经病变。为了治疗异常的眼压升高，我们研究了房水流出阻力，这是眼压升高的关键因素。我们检查了岩石抑制剂的药理作用，它降低了房水阻力。用培养的小梁细胞进行的实验表明，ROCK抑制剂诱导细胞黏附增强，细胞骨架松弛，细胞外基质结构改变。此外，我们对健康志愿者的临床试验表明，ROCK抑制剂显著降低了人眼的眼压，而没有严重的副作用。这项用兔眼进行的实验表明，滤过性手术后，ROCK抑制剂持续降低眼压，这是青光眼的一项主要手术程序。因此，我们引入了ROCK抑制剂作为新的抗青光眼药物，并启发了一种通过生理性房水途径降低眼压的新策略。此外，我们还研究了继发性青光眼的发病机制，继发性青光眼也是由房水流出阻力增加引起的。曲安奈德是一种广受欢迎的皮质类固醇药物，可高度诱导激素性青光眼。我们报道的激素性青光眼的危险因素是年龄小、基线眼压高、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，家族性淀粉样变性是一种遗传性疾病，在日本熊本市发病率很高。

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.