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

发育性、年龄相关性和遗传性脉络膜视网膜疾病的病因研究和新疗法

基本信息

批准号：
18390466
负责人：
TERASAKI Hiroko
金额：
$ 10.5万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390466/
关键词：
age-related macular degeneration gene polymorphism photodynamic therapy autosomal dominant optic atrophy retinal regeneration retinal pigment epithelium transplantation retinitis pigmentosa transgenic rabbit 網膜変性網膜色素変性

项目摘要

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

在这两年中，我们继续阐明和创造新的治疗方法的绒毛膜视网膜疾病。首先，我们证实了补体因子Y402H多态性与年龄相关性黄斑变性（AMD）和息肉样脉络膜血管病变（PCV）的发病有关，并且在AMD和PCV的参与者中，活性蛋白（CRP） 1水平显著升高（Ophthalmology, 2007）。然后我们发现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CRP水平升高，表明AMD和PCV与炎症密切相关（ARVO, 2008）。另一方面，AMD和PCV患者接受光动力治疗（PDT）时，由于绒毛膜视网膜循环减少，视网膜功能出现短暂性下降（IOVS, 2007）。然而，PDT和药物联合治疗可以预防黄斑功能下降，并且玻璃体内注射抗血管生成药物可以增加黄斑功能（ARVO, 2008）。第二，与名古屋大学工程学院合作研究视网膜色素上皮自体移植治疗AMD。我们发现磁性颗粒被有效地吸收到ARPE19细胞中，并加速了质粒在细胞中的整合。此外，我们证实磁性细胞可以在体外使用磁铁进行引导（ARVO,2008）。在遗传疾病的研究中，我们精确地研究了常染色体显性视神经萎缩的基因型和表型特征（ADOA; Ophthalmology,2006）。在本研究中，我们使用视网膜电图和光学相干断层扫描检测视网膜内异常（IOVS, 2007）。在动物基础研究中，我们发现小鼠纤毛体中存在能够光感受器再生的生发带（IOVS, 2007）。此外，注射血管内皮生长因子（VEGF； IOVS, 2007）和视网膜脱离（IOVS, 2008）可以保存遗传进展性光感受器变性的rd1小鼠的光感受器。此外，我们还成功地创造了第一个中型动物作为视网膜色素变性的模型。我们将视紫红质突变基因Pro347Leu诱导到家兔体内，制备了具有遗传性光感受器变性的转基因家兔。我们通过组织学和电生理分析证实了该模型的进行性光感受器变性（ARVO, 2008）。少

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Abnormalities of visual-evoked potentials and pupillary light reflexes in a family with autosomal dominant occult macular dystrophy.

常染色体显性隐匿性黄斑营养不良家系的视觉诱发电位和瞳孔对光反射异常。

DOI：
发表时间：
2007
期刊：
Clin Exp Ophthalmol 35
影响因子：
0
作者：
Koyasu;T;Nakamura Y.(et al);Miyata K.(et al);Kurimoto T.(et al);Nishiguchi KM.(et al);Kaneko H.(et al);Kondo M.(et al);Hood DC.(et al);Koyasu T.(et al);Koike C.(et. al.);Kikuchi M.(et. al.);Ishikawa K.(et. al.);Ikenoya K.(et. al.);Nishiguchi KM.(et. al.);Ito Y.(et. al.);Yata T.(et. al.);Okuno T.(et. al.)
通讯作者：
Okuno T.(et. al.)

Effect of axial length on laser spot size during photodynamic therapy : an experimental study in monkeys

光动力治疗期间轴长对激光光斑大小的影响：猴子的实验研究