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Investigation of the molecular mechanism of glaucoma and gene therapy for the treatment of glaucoma

青光眼分子机制研究及青光眼基因治疗

基本信息

批准号：
10470362
负责人：
KASHII Satoshi
金额：
$ 8.13万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

In glaucomatous eyes, abnormally increased intraocular pressure (IOP) induces retinal ganglion cell death, resulting in loss of visual acuity. At present, most of the drugs and surgeries for glaucoma have been developed for lowering IOPs. Our experimental studies are aimed to protect the cell death of retinal ganglion cells, "neuroprotective therapy, "and repair the damaged axons, "neuroregenerative therapy." In an attempt to rescue retinal ganglion cells from cell death, we investigated the neuroprotective effects of neurotrophic factors in animal glaucomatous models. Our immunohistochemical analyses showed that, in the retinal tissues of animal glaucomatous models, Muller glial cells and astrocytes were activated, and one of neurotrophic factors, ciliary neurotrophic factor (CNTF), was secreted from these glial cells. Moreover, two types of neurotrophic factors, ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) showed neuroprotective effects for retinal ganglion cells in animal glaucomatous models. In addition, we demonstrated that two types of chondroitin sulfate proteoglycans (CSPGs), neurocan and phosphacan, were highly expressed in the developing retina. Furthermore, the CSPGs regulated the neurite outgrowth from retinal ganglion cells in vitro, indicating the possibility that the neuroregenerative therapy can be achieved by controlling the expression of the CSPGs. Our investigations will play important roles in developing the new concepts of the treatment for glaucoma.

在青光眼眼中，异常升高的眼压（IOP）会导致视网膜神经节细胞死亡，导致视力丧失。目前，大多数治疗青光眼的药物和手术都是为了降低眼压。我们的实验研究旨在保护视网膜神经节细胞的细胞死亡，即“神经保护疗法”，以及修复受损的轴突，即“神经再生疗法”。为了拯救视网膜神经节细胞免于细胞死亡，我们研究了神经营养因子在动物青光眼模型中的神经保护作用。我们的免疫组织化学分析表明，在动物青光眼模型的视网膜组织中，Muller 胶质细胞和星形胶质细胞被激活，并且这些胶质细胞分泌神经营养因子之一，睫状神经营养因子（CNTF）。此外，两种类型的神经营养因子，睫状神经营养因子（CNTF）和脑源性神经营养因子（BDNF）在动物青光眼模型中显示出对视网膜神经节细胞的神经保护作用。此外，我们还证明了两种类型的硫酸软骨素蛋白聚糖（CSPG）：神经聚糖和磷酸聚糖，在发育中的视网膜中高度表达。此外，CSPG在体外调节视网膜神经节细胞的神经突生长，表明可以通过控制CSPG的表达来实现神经再生治疗。我们的研究将在开发青光眼治疗新概念方面发挥重要作用。