The development and clinical application of molecular-based new medical treatments for glaucoma

本研究旨在探讨青光眼眼压升高和视神经损害的分子机制，为青光眼的药物治疗提供新的思路。我们展示了手术重建房水流出道的临床结果，以研究房水流出道阻力（Arch Ophthalmol 2004）。然后，我们检查了青光眼的遗传分析，以确定遗传学与房水流出阻力之间的关系（Exp Cell Res 2004 ; IOVS 2004 ; J Glaucoma 2004 ; Mol维斯2005）。此外，我们阐明了淀粉样蛋白诱导的继发性青光眼的分子机制，这是来自一个单一的基因突变。我们报道了突变型甲状腺素运载蛋白在眼组织中的定位、眼部并发症临床治疗的困难以及基因治疗的可能性（Transplantation 2004 ; Gene Therapy 2004 ; Amyloid 2004 ; Exp Eye Res 2005 ; Ophthalmology 2005）。此外，我们研究了ROCK抑制剂对小梁网细胞的药理学作用，该抑制剂可降低房水流出阻力（Exp Eye Res 2006）。另一方面，我们显示了白细胞和内皮细胞之间的相互作用在眼部疾病中的病理学意义，并且显示了相互作用的抑制诱导视网膜组织中的神经保护作用（IOVS 2004 ; Arch Ophthalmol 2004 ; Pro Natl Acad Sci USA，2003）。我们还表明，眼睛在病理条件下表达生物活性因子，也导致神经保护作用（NeuroReport 2004），并且内质网中的应激反应在神经保护中起重要作用（J Neurochem 2006）。

We investigated molecular mechanisms of intraocular pressure elevation and optic nerve damage in glaucoma to develop new medical treatment for glaucoma. We showed the clinical results about surgical reconstruction for aqueous outflow to investigate aqueous outflow resistance (Arch Ophthalmol 2004). Then, we examined genetic analyses of glaucoma to identify the relationship between the genetics and the aqueous outflow resistance (Exp Cell Res 2004 ; IOVS 2004 ; J Glaucoma 2004 ; Mol Vis 2005). In addition, we elucidated the molecular mechanism of amyloid-induced secondary glaucoma, which is derived from a single gene mutation. We reported the localization of mutant transthyretin in ocular tissues, the difficulties in clinical treatments for the ocular complications and the possibility of the gene therapy (Transplantation 2004 ; Gene Therapy 2004 ; Amyloid 2004 ; Exp Eye Res 2005 ; Ophthalmology 2005). Moreover, we investigated the pharmacologic effect of ROCK inhibitor, which reduces the aqueous outflow resistance, for trabecular meshwork cells (Exp Eye Res 2006). On the other hand, we showed the pathological significance of the interaction between leukocytes and endothelium in eye diseases, and showed that the inhibition of the interaction induces the neuroprotective effect in retinal tissues (IOVS 2004 ; Arch Ophthalmol 2004 ; Pro Natl Acad Sci USA, 2003). We also showed that the eye in pathological conditions expresses bioactive factors, also resulting in neuroprotective effects (NeuroReport 2004), and that the stress response in endoplasmic reticula plays an important role in neuroprotection (J Neurochem 2006).