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

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。

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.