MOLECULAR MECHANISMS OF SIGNAL TRANSDUCTION IN RETINA

视网膜信号转导的分子机制

• 批准号: 7958470
• 负责人: Brett G Jeffrey
• 金额: $ 10.04万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-04 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958470
• 关键词: Acids; Brain; Cells; Computer Retrieval of Information on Scientific Projects Database; Cornea; Defect; Development; Disease; Electrodes; Electroretinography; Funding; GTP-Binding Proteins; Glutamates; Grant; Human; Institution; Knowledge; Light; Measures; Mediating; Molecular; Neurotransmitters; Primates; Research; Research Personnel; Resources; Retina; Retinal; Role; Signal Pathway; Signal Transduction; Source; United States National Institutes of Health; Vertebrate Photoreceptors; Visual; Visual Pathways; ganglion cell; in vivo; insight; ligand gated channel; metabotropic glutamate receptor 4; receptor; response; retinal rods; voltage

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. In preliminary studies 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 谷氨酸是视网膜中的主要兴奋性神经递质，沿着从杆和锥到双极细胞以及从这些细胞到神经节细胞和大脑的视觉途径使用。谷氨酸刺激两类受体：离子配体门控通道和G蛋白偶联的mglurs。 III组MGLURS是由L-2-Amino-4-膦酰丁酸（APB）选择激活的相关mglurs的子集，由MGLUR4，-R6，-R7和-R8组成。除了介导双极细胞对光线的去极化响应的MGLUR6外，视网膜中其他mglurs的功能仍然不确定。在初步研究中，我们发现MGLUR4，-R7和-R8位于视网膜近端。可以用电子图（ERG）评估视网膜功能，这是响应从角膜电极记录的光中响应视网膜电压变化的度量。当前研究的目的是确定III II II MGLUR在用ERG测量的内部视网膜信号传导中的作用。现在已经知道了棒光感受器中G蛋白信号传导的蛋白质和受体，并且两者中的缺陷都与人类的视觉缺陷有关。对内部视网膜内的信号通路的更好理解应提供对其他视觉缺陷的原因的更深入的了解。这些知识将为开发以前无法治疗的视觉疾病开发新疗法铺平道路。