MOLECULAR MECHANISMS OF SIGNAL TRANSDUCTION IN RETINA

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级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，沿着视觉通路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。谷氨酸刺激两类受体：离子亲和性配体门控通道和G蛋白偶联的mGluRs。第三组mGluRs是由L-2-氨基-4-膦酸丁酸选择性激活的相关mGluR的一个子集，由mGluR4、-R6、-R7和-R8组成。除了mGluR6介导双极细胞对光的去极化反应外，其他mGluR在视网膜中的功能仍不明确。我们发现mGluR4、-R7和-R8定位于视网膜近端。视网膜功能可以用视网膜电信号(ERG)在活体内进行评估，ERG是一种测量视网膜两端的电压对角膜电极记录的光的反应的变化。目前这项研究的目的是确定 视网膜电信号测试显示，第三组mGluRs在视网膜内信号中的作用。杆状感光器中参与G蛋白信号传递的蛋白质和受体现在已被详细了解，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部的信号通路应该能更好地洞察其他视觉缺陷的原因。这一知识将为开发以前无法治愈的视觉疾病的新疗法铺平道路。我们发现mGluR4缺陷小鼠有异常的明视ERG，具有更大和更长的振荡电位。我们认为mGluR4受体调节从无长突细胞到双极细胞的反馈。

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.