• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Brain-derived neurotrophic factor promotes retinal ganglion cell survival and reduces tyrosine receptor kinase B protein andmRNA in vivo.
【24h】

Brain-derived neurotrophic factor promotes retinal ganglion cell survival and reduces tyrosine receptor kinase B protein andmRNA in vivo.

机译：脑源性神经营养因子在体内可促进视网膜神经节细胞存活并减少酪氨酸受体激酶B蛋白和mRNA。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Glaucoma is a disease of the visual system that often is characterized by elevated intraocular pressure, compressive damage to optic nerve (ON), and a loss of ganglion cells within the retina. Since direct mechanical damage to the ON also results in a progressive loss of ganglion cells, ON crush is commonly used as a model to evaluate treatment strategies for different retinal disorders. Brain-derived neurotrophic factor (BDNF) has been shown to be one of the most effective neuroprotectants in the rat eye, a fact confirmed by the present studies (94% survival rate in treated eyes).; Since the rodent and primate eyes differ in many respects, a cat optic nerve crush model was developed as an intermediate test of whether BDNF might also serve as an effective neuroprotectant in primate-sized eyes. Here, treatment with 15, 30, 60, and 90μg of BDNF at the time of the ON crush resulted in ganglion cell survival rates of 52%, 81%, 77%, and 70%, respectively. Cell size comparisons showed that 30μg saved a wider range of ganglion cells, while 90μg minimized the loss of medium-sized neurons and retained normal proportions of large, medium, and small ganglion cells.; To test whether Müller cells, the primary glia of the retina, are affected by ON injury or are involved in BDNF-mediated responses, two glia specific proteins were studied. Glia fibrillary acidic protein (GFAP) increased ∼7–9 fold 3 days post ON crush and remained elevated for the 2 week period examined. Glutamine synthetase (GS), an enzyme typically located within Müller cell bodies, showed a temporary shift from the cell soma to the Müller endfeet of the inner retina within 24 hours. The change was not accompanied by an increase in total GS protein. BDNF, however, did not affect GFAP or GS levels, suggesting that Müller cells do not contain BDNF receptors.; The biological effects of BDNF are mediated primarily by its high affinity receptor tyrosine kinase B. Although this receptor is present in both truncated and full length form, it is the full length receptor (TrkB-FL) that is responsible for initiation of the intracellular signaling cascade that underlies the neuroprotective role of BDNF. Interestingly, intravitreal application of BDNF results in a rapid, dramatic, and long lasting reduction in TrkB-FL protein in the normal rat retina; only 4.8% and 31.4% of protein remains at 1 and 14 days post-injection, respectively. Optic nerve crush reduced TrkB-FL protein 14 days post-crush. When BDNF is applied at the time of the ON nerve crush, TrkB-FL protein decreases to levels similar to that seen in animals receiving the BDNF injection alone. These data suggest that the failure to enhance RGC survival in the cat via multiple injections of BDNF most likely resulted from a BDNF-induced reduction in the overall level of full length receptors within those eyes. In all cases, the changes in TrkB-FL protein were accompanied by changes in TrkB-FL mRNA levels as well. The pattern of change in TrkB-FL mRNA followed a bell-shaped curve, with that measured on days 1 and 14 below normal. In summary, these results provide encouraging data indicating that BDNF is a potential neuroprotectant for use in glaucoma patients.
机译：青光眼是一种视觉系统疾病，通常特征在于眼内压升高，视神经（ON）压缩性损伤以及视网膜内神经节细胞的丢失。由于对ON的直接机械损伤也会导致神经节细胞的逐渐丢失，因此ONrush通常被用作评估不同视网膜疾病治疗策略的模型。脑源性神经营养因子（BDNF）已被证明是大鼠眼中最有效的神经保护剂之一，这一事实已被本研究证实（治疗眼的存活率为94％）。由于啮齿动物的眼睛和灵长类动物的眼睛在许多方面都存在差异，因此开发了猫视神经挤压模型作为BDNF是否也可以作为灵长类动物大小的眼睛的有效神经保护剂的中间测试。在这里，在ON压迫时用15、30、60和90μgBDNF进行处理可使神经节细胞存活率分别达到52％，81％，77％和70％。细胞大小比较显示，30μg可以保存更广泛的神经节细胞，而90μg可以最大程度地减少中型神经元的损失，并保持大，中，小神经节细胞的正常比例。为了测试视网膜原代神经胶质Müller细胞是否受到ON损伤的影响或是否参与BDNF介导的反应，研究了两种神经胶质特异性蛋白。挤压后3天，胶质纤维酸性蛋白（GFAP）增加了约7-9倍，并且在检查的2周期间一直保持升高。谷氨酰胺合成酶（GS）是一种通常位于Müller细胞体内的酶，在24小时内显示出从细胞体到内部视网膜Müller末端的暂时转移。该变化不伴有总GS蛋白的增加。然而，BDNF并不影响GFAP或GS的水平，表明Müller细胞不包含BDNF受体。 BDNF的生物学效应主要由其高亲和力受体酪氨酸激酶B介导。尽管该受体以截短和全长形式存在，但全长受体（TrkB-FL）负责细胞内信号传导的启动。级联是BDNF的神经保护作用的基础。有趣的是，玻璃体腔内应用BDNF可导致正常大鼠视网膜中TrkB-FL蛋白迅速，戏剧性且持久地减少。注射后1天和14天分别仅保留蛋白质的4.8％和31.4％。视神经挤压后14天减少了TrkB-FL蛋白。当在ON神经压迫时应用BDNF时，TrkB-FL蛋白的水平降低到与仅接受BDNF注射的动物相似的水平。这些数据表明，通过多次注射BDNF未能提高猫的RGC存活率，很可能是由于BDNF诱导了这些眼睛中全长受体的总体水平降低所致。在所有情况下，TrkB-FL蛋白的变化也伴随着TrkB-FL mRNA水平的变化。 TrkB-FL mRNA的变化模式遵循钟形曲线，在正常水平的第1天和第14天测得。总之，这些结果提供了令人鼓舞的数据，表明BDNF是用于青光眼患者的潜在神经保护剂。

著录项

  • 作者

    Chen, Hao.;

  • 作者单位

    Michigan State University.;

  • 授予单位 Michigan State University.;
  • 学科 Biology Neuroscience.; Biology Anatomy.
  • 学位 Ph.D.
  • 年度 2001
  • 页码 111 p.
  • 总页数 111
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经科学;生物形态学;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号