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Molecular Biological Study on Mechanism of Neuronal Cell Death and Establishment of New Therapy in Glaucoma

青光眼神经细胞死亡机制的分子生物学研究及新疗法的建立

基本信息

批准号：
12671699
负责人：
ABE Haruki
金额：
$ 2.24万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671699/
关键词：
NMDA receptor glutamate knockout mice ischemia-reperfusion model retinal ganglion cell glaucoma brain-derived neurotrophic factor 網膜眼圧ラット神経節細胞 ε1サブユニット ε2サブユニット

项目摘要

Cell death has been thought to be induced by glutamate that stimulates the N-methyl-d-aspatate (NMDA) receptor present on retinal ganglion cells and on cells in the inner nuclear layer. Knock out mice were used to elucidate the role of the NR2A and NR2B subunit of the NMDA receptor. Wild type and NR2A and NR2B subunit knock out mice were used. Transient retinal ischemia was induced by raising intraocular pressure (IOP) to 120mmHg. In the Wild type mice, all the retinal ganglion cells were lost after 14 days. The number of cells in the inner nuclear layer was decreased. The thickness of the inner plexiform layer was reduced. By contrast, the retina appeared to be normal, unaffected by the insult in the NR2A subunit knockout mice. While the NR2B subunit knock out mice also showed the same tendency. These results suggest that the subunit may have a direct role in the retinal cell death induced by ischemia-reperfusion.We quantifies the level of brain-derived neurotrophic factor (BDNF) in the retina of experimental ocular hypertension model rat. To induce unilateral IOP elevation, we used a model developed by Ueda et al. (1998). Fellow eyes were served as control. IOP was measured by pneumatonometer. After the duration of IOP elevation above 22 mmHg for 1, 2, 4 and 12 weeks, retinas were dissected out from both experimental and control eyes and used as samples. To quantify BDNF protein level, we used enzyme-linked immunosorbant assay. Retinal BDNF levels of hypertensive eye compared to control after 1, 2, 4 and 12 weeks of IOP elevation were 277%, 102%, 59% and 24%, respectively. This study clarifies that BDNF levels were dramatically altered in the retina of experimental ocular hypertension model rat.

细胞死亡被认为是由谷氨酸诱导的，谷氨酸刺激存在于视网膜神经节细胞和内核层细胞上的N-甲基-d-天冬氨酸(NMDA)受体。基因敲除小鼠被用来阐明NMDA受体的NR2A和NR2B亚单位的作用。采用野生型及NR2A型和NR2B型基因敲除小鼠。将眼压升高至120毫米汞柱，诱发一过性视网膜缺血。野生型小鼠14天后视网膜神经节细胞全部消失。内核层细胞数量减少。内层网状层的厚度减小。相比之下，在NR2A亚单位基因敲除小鼠中，视网膜似乎是正常的，没有受到侮辱的影响。而NR2B亚单位基因敲除小鼠也表现出同样的趋势。这些结果表明该亚单位可能在缺血再灌流诱导的视网膜细胞死亡中起直接作用。我们对实验性高眼压模型大鼠视网膜中脑源性神经营养因子(BDNF)的水平进行了定量。为了诱导单侧眼压升高，我们使用了上田等人开发的模型。(1998年)。对侧眼作为对照。用气压计测量眼压。眼压升高持续1、2、4、12周后，分别从实验眼和对照眼取出视网膜作为标本。采用酶联免疫吸附试验对BDNF蛋白水平进行定量。眼压升高1周、2周、4周和12周时，高血压眼视网膜BDNF水平分别为277%、102%、59%和24%。本研究阐明了实验性高眼压模型大鼠视网膜中BDNF水平的显著变化。