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

在这两年中，我们致力于阐明和创造治疗脉络膜视网膜疾病的新方法。首先，我们证实补体因子H Y402H基因多态性与老年性黄斑变性和息肉状脉络膜血管病的发病有关，并且在老年性黄斑变性和息肉脉络膜血管病的参与者中，L的C反应蛋白水平显著升高(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，携带HTRA1和LOC387715启动子风险等位基因的个体的CRP水平升高，这表明AMD和PCV与炎症密切相关(Arvo，2008)。另一方面，接受光动力学治疗(PDT)的AMD和PCV患者显示出由于脉络膜视网膜循环减少而导致的一过性视网膜功能下降(IOVS，2007)。然而，光动力疗法和药物…的联合治疗第二，与名古屋大学工程学院合作进行的旨在通过自体视网膜色素上皮移植治疗AMD的研究。我们发现磁性颗粒有效地被ARPE19细胞摄取，并加速了细胞对质粒的掺入。在遗传性疾病的研究中，我们精确地研究了常染色体显性遗传性视神经萎缩(ADOA；眼科，2006)的基因和表型特征。在本研究中，我们利用视网膜电信号和光学相干断层扫描(IOVS，2007)检测了视网膜内的异常。在动物基础研究中，我们发现小鼠睫状体中存在能够光感受器再生的生发区(IOVS，2007)。此外，通过注射血管内皮生长因子(血管内皮生长因子；IOVS，2007)和视网膜脱离(IOVS，2008)，可以保存遗传进行性感光细胞退化的Rd1小鼠的光感受器。此外，我们还成功地制作了第一只中型动物AS--视网膜色素变性模型。我们将视紫红质基因突变(Pro347Leu)导入兔体内，获得了遗传性光感受器变性的转基因兔。我们用组织学和电生理学分析证实了这种模型中的进行性光感受器退化(Arvo，2008)。较少

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