MOLECULAR MECHANISMS OF SIGNAL TRANSDUCTION IN RETINA

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 谷氨酸是视网膜中主要的兴奋性神经递质，沿着从视杆细胞和视锥细胞到双极细胞，再从这些细胞到神经节细胞和大脑的视觉通路使用。谷氨酸刺激两类受体：离子型配体门控通道和G蛋白偶联mGluRs。III组mGluR是由L-2-氨基-4-膦酰基丁酸（APB）选择性激活的相关mGluR的子集，由mGluR 4、-R6、-R7和-R8组成。除了mGluR 6介导ON双极细胞对光的去极化反应外，视网膜中其他mGluRs的功能尚不清楚。我们发现mGluR 4、-R7和-R8位于近端视网膜内。视网膜功能可以用视网膜电图（ERG）在体内评估，视网膜电图是响应于从角膜电极记录的光的跨视网膜的电压变化的量度。目前研究的目的是确定 用ERG测量的III组mGluR在内视网膜信号传导中的作用。在视杆细胞中参与G蛋白信号传导的蛋白质和受体现在已经被详细了解，两者的缺陷都与人类的视觉缺陷有关。更好地了解视网膜内层的信号通路应该提供更深入的了解其他视觉缺陷的原因。这些知识将为开发以前无法治疗的视觉疾病的新疗法铺平道路。我们发现mGluR 4缺陷小鼠具有异常的明视ERG，具有更大和更长的振荡电位。 我们建议，mGluR 4受体调节反馈从无长突双极细胞。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Glutamate is the main excitatory neurotransmitter in the retina, used along the visual pathway from rods and cones to bipolar cells, and from these to ganglion cells and to the brain. Glutamate stimulates two classes of receptors: ionotropic ligand-gated channels and G protein-coupled mGluRs. Group-III mGluRs are a subset of related mGluRs selectively activated by L-2-amino-4-phosphonobutyric acid (APB) and consist of mGluR4, -R6, -R7, and -R8. Except for mGluR6, which mediates the depolarizing response of ON-bipolar cells to light, the function of the other mGluRs in the retina remains undefined. We found that mGluR4, -R7, and -R8 are localized within the proximal retina. Retinal function may be assessed in-vivo with the electroretinogram (ERG), a measure of the change in voltage across the retina in response to light recorded from corneal electrode. The aim of the current research was to determine the role of group-III mGluRs in inner retinal signaling as measured with the ERG. The proteins and receptors involved in G-protein signaling in rod photoreceptors are now known in detail and defects in both have been associated with visual defects in humans. A better understanding of the signaling pathway within the inner retina should provide greater insight into the causes of other visual defects. This knowledge would pave the way for development of new therapies for previously untreatable visual diseases. We found that mGluR4 deficient mice have abnormal photopic ERGs, with larger and more prolonged oscillatory potentials. We propose that the mGluR4 receptor modulates feedback from amacrine to bipolar cells.