MOLECULAR MECHANISMS OF SIGNAL TRANSDUCTION IN RETINA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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测量。目前研究的目的是确定III组mGluRs在视网膜内信号传导中的作用，如用ERG测量的。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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 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.