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

青光眼房水流出分子机制的研究及眼压升高治疗新方法的探索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视神经病变。为了治疗异常眼压升高，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ROCK抑制剂的药理作用，它可以降低房水耐药性。用培养的小梁网细胞进行的实验表明，ROCK抑制剂能增强细胞粘附，松弛细胞骨架，改变细胞外基质的结构。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眼压，且无严重副作用。兔眼实验表明，ROCK抑制剂在青光眼主要手术滤过术后保持眼压降低。因此，我们引入ROCK抑制剂作为新的抗青光眼药物，并启发了通过生理房水通路降低眼压的新策略。此外，我们研究了继发性青光眼的发病机制，这也是由房水流出阻力增加引起的。曲安奈德是一种常用的皮质类固醇药物，可高度诱导类固醇性青光眼。我们报道了类固醇性青光眼的危险因素是年龄小、基线眼压高、玻璃体内注射曲安奈德和大剂量注射曲安奈德。最后，我们报道了继发性青光眼与家族性淀粉样变相关的手术后并发症，这是一种遗传性疾病，在日本熊本表现出很高的患病率。

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.