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The quantitative analyses of electroretinogram and histology for retinal degeneration using transgenic mice

转基因小鼠视网膜变性的视网膜电图和组织学定量分析

基本信息

批准号：
14571676
负责人：
GOTO Yoshinobu
金额：
$ 2.24万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571676/
关键词：
retinal degeneration transgenic models electroretinogram rods cones function of inner layer of retina dark reared gene therapy 網膜色素変成症 CMYCマウス杆体細胞細胞変性網膜内層網膜色素変性症杵体細胞錐体細胞 ON型,OFF型双極細胞律動様小波

项目摘要

The electrophysiological dysfunction of retina in retinitis pigmentosa should be caused by the retinal cells degeneration. The purposes of this project were to clarify the mechanism of this dysfunction and to advocate the new treatment in retinitis pigmentosa using the transgenic mouse and rat models. To address these issue, we quantitatively analyzed the electroretinograms and the histopathological changes of retina to evaluate the functional changes of rods, cones and inner cell layer in each transgenic mouse. We also compared the retinal functions between cyclic-light-reared and dark-reared mice to evaluate the retinal damages by the light. In addition, we transplanted the growth factor gene in subretina using the viral vector, and analyzed the protecting effects from the retinal degeneration. Our results were summarized as follows ; 1)the functions of ON- and OFF- bipolar cells in CMYC mouse were kept until 1 month, but disappeared at 6 month, 2)the dysfunctions of inner layer of r … More etina in each transgenic animal were started at earlier than the histological changes, 3)the dark-reared for 3 months was slowed the retinal degeneration in CMYC mouse, 4)the protecting effects for retinal functions by gene transplantation was observed in res rats (Ikeda et al.,2003;Miyazaki et al.,2003), and 5) there was not statistically significant the protecting effects for retinal functions by gene transplantation in dark-reared CMYC mouse. Overall, our findings suggest that the functional changes of rods, cones, and inner layers of retina were caused by the retinal cell degenerations. According to the new treatment, at present, the decrement of the light should be the first choice to protect the remaining functions of retina in retinal degeneration disease. In addition, the gene therapy should become a good treatment for this disease in near future, however we must improve the more practical methods of the vector transplantation to the retina. Finally, we could get the beneficial results at this project for the mechanism of functional decrements of retina and the treatment for the retinal degeneration in retinitis pigmentosa. Less

视网膜色素变性的视网膜电生理功能障碍可能是由视网膜细胞变性引起的。本项目的目的是阐明这种功能障碍的机制，并利用转基因小鼠和大鼠模型倡导治疗视网膜色素变性的新方法。为了解决这些问题，我们定量分析了视网膜电信号和视网膜的组织病理学变化，以评估每个转基因小鼠的视杆细胞、视锥细胞和内细胞层的功能变化。我们还比较了周期光饲养和暗饲养小鼠的视网膜功能，以评估光对视网膜的损害。此外，我们还利用病毒载体将生长因子基因移植到视网膜下，并分析了其对视网膜变性的保护作用。我们的研究结果如下：1)cmyc小鼠的开、离双极细胞功能维持到1个月，6个月后消失；2)r…内层功能障碍。3)暗饲养3个月的cMYC小鼠延缓了视网膜的变性，4)基因移植对Res大鼠视网膜功能有保护作用(Ikeda等，2003；Miyazaki等，2003)，5)暗饲养cMYC小鼠基因移植对视网膜功能的保护作用无统计学意义。总体而言，我们的发现表明，视网膜视杆细胞、视锥细胞和内层的功能变化是由视网膜细胞退化引起的。根据新的治疗方法，目前，在视网膜变性疾病中，光的减少应该是保护视网膜剩余功能的首选。此外，基因治疗在不久的将来应该成为治疗该病的好方法，但我们还需要改进更实用的视网膜载体移植方法。最后，对视网膜功能减退的机制和治疗视网膜色素变性的研究取得了有益的结果。较少