Investigation of pathogenegs and new treatment for developmental, age-related and inherited chorioretinal diaasse

在这两年中，我们继续阐明和创造脉络膜视网膜疾病的新疗法。首先，我们证实补体因子 H Y402H 多态性与年龄相关性黄斑变性 (AMD) 和息肉状脉络膜血管病变 (PCV) 的发病有关，并且患有 AMD 和 PCV 的参与者的活性蛋白 (CRP)l 水平显着较高 (O眼科，2007)。随后我们发现HTRA1和LOC387715启动子的单核苷酸多态性与AMD和PCV的发病有关。此外，具有HTRA1和LOC387715启动子风险等位基因的个体表现出CRP水平升高，这表明AMD和PCV与炎症密切相关(ARVO，2008)。另一方面，接受光动力治疗(PDT)的AMD和PCV患者由于脉络膜视网膜循环减少而出现短暂的视网膜功能下降(IOVS，2007)。然而，PDT和Pharmaceutical的联合治疗能够防止黄斑功能下降，玻璃体内注射抗血管生成药物可以增加黄斑功能（ARVO，2008）其次，与名古屋大学工程学院的合作研究旨在通过自体视网膜色素上皮移植治疗AMD。我们发现 ARPE19 细胞可以有效吸收磁性颗粒并加速质粒的细胞掺入。此外，我们还证实磁性细胞可以在体外利用磁体进行引导（ARVO，2008）。在遗传性疾病研究中，我们精确研究了常染色体显性视神经萎缩的基因型和表型特征（ADOA；眼科，2006）。在这项研究中，我们利用视网膜电图和光学相干断层扫描检测了视网膜内部的异常（IOVS，2007）。在基础研究中通过动物实验，我们发现小鼠睫状体内存在能够进行光感受器再生的生发区（IOVS，2007）。此外，具有遗传性感光细胞变性的rd1小鼠的感光细胞可以通过注射血管内皮生长因子（VEGF；IOVS，2007）和视网膜脱离（IOVS，2008）来保存。此外，我们还首次成功创建了中型动物视网膜色素变性模型。我们在兔子体内诱导了视紫红质突变（Pro347Leu），并创造了具有遗传性光感受器变性的转基因兔子。我们使用组织学和电生理学分析证实了该模型中的渐进性感光器变性（ARVO，2008）。较少的

During these two years, we proceeded for elucidating and creating new treatment for chorioretinal diseases. First, we confirmed that complement factor H Y402H polymorphism was related to the onset of age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV), and Creactive protein (CRP)l levels were significantly higher in the participants with AMD and PCV (Ophthalmology, 2007). Then we identified that single nucleotide polymorphism in the promoter of HTRA1 and LOC387715 were related to the onset of AMD and PCV. Furthermore, the individuals with the risk allele of promoter of HTRA1 and LOC387715 showed the increase levels of CRP level, which indicated AMD and PCV were closely related to the inflammations (ARVO, 2008) .On the other hand, the patient with AMD and PCV who received photodynamic therapy (PDT) showed transient decrease of retinal function caused by the reduced chorioretinal circulation (IOVS, 2007). However, the combination therapy with PDT and pharma … More ceutical enabled to prevent the reduced macular function, and intravitreous injection of anti-angiogenic drugs increased macular function (ARVO, 2008)Second, the collaborative research with Nagoya University, School of Engineering aimed for the treatment of AMD with autologous transplantation of retinal pigment epithelium. We identified efficient uptake of magnetic particles into ARPE19 cells and accelerated cell incorporation of plasmid. Moreover, we confirmed that magnetic cells could be guided using magnet in vitro (ARVO,2008) .In the research on inherited diseases, we studied precisely the genotypic and phenotypic features of autosomal dominant optic atrophy (ADOA ; Ophthalmology,2006) .In this research, we detected the abnormality of inner retina using electroretinograms and optical coherence tomography (IOVS, 2007) .In the basic research using animals, we found the existence of germinal zone capable of photoreceptor regeneration in the mouse ciliary body (IOVS, 2007). In addition, the photoreceptors of rd1 mice which has genetically progressed photoreceptor degeneration could be preserved with injection of vascular endothelial growth factor (VEGF; IOVS, 2007) and retinal detachment (IOVS, 2008). Moreover, we succeeded the first creation of middle-sized animal as, a model of retinitis pigmentosa. We induced the rhodopsin mutation (Pro347Leu)into the rabbit and created transgenic rabbit which has genetic photoreceptor degeneration. We confirmed progressive photoreceptor degeneration in this model using histological and electrophysiological analysis (ARVO, 2008). Less