THE ROLE OF TAURINE AND GABA IN MAMMALIAN RETINA

牛磺酸和 GABA 在哺乳动物视网膜中的作用

• 批准号: 3260421
• 负责人: JANG-YEN WU
• 金额: $ 12.31万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1988-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3260421
• 关键词: antiserum; autoradiography; decarboxylases; electron microscopy; embryo /fetus; gamma aminobutyrate; glutamate decarboxylase; histochemistry /cytochemistry; immunochemistry; ligands; mammalian embryology; mature animal; microscopy; neurons; newborn animals; retina; retina disorder; synapses; taurine

The overall objective of the proposed project is to elucidate the role of taurine and Gamma-aminobutyric acid (GABA) in mammalian retina. More specifically, we plan to perform the following studies: 1. To identify GABA-containing and taurine-containing neurons and their processes and to analyze the synaptic circuitry of these neurons in retina by localizing their respective synthesizing enzymes, namely, L-glutamic acid decarboxylase (GAD) for GABA and cysteinesulfinic acid decarboxylase (CSAD) for taurine using light and electron microscopic (EM) immunocytochemical methods with specific anti-GAD and anti-CSAD sera, respectively. 2. To elucidate the mechanism by which the functions of GABA and taurine in retina are regulated. One such mechanism is the potentiation of GABA action by benzodiazepine (BDZP). Hence, the precise cellular and subcellular distribution of BDZP receptor and its endogenous ligands in retina will be determined with a special emphasis on the relationship between BDZP and GABA system. 3. To localize taurine- and GABA-accumulating and taurine- and GABA-receptive processes by EM autoradiography, following both in vivo and in vitro exposure of retina to radioactively-labeled GABA and taurine and their analogues. 4. To determine the developmental sequence of GABAergic system and taurine-containing neurons and the role of taurine and GABA in the development of retinal function. The following parameters will be analyzed at various developmental stages, e.g., in embryonic stages, newborn, during active synaptogenesis and at adult in order to determine the sequence of events that appears during retinal development: (a) the GABA- and taurine-synthesizing activities, namely, GAD and CSAD activities and their precise cellular and subcellular locations (presynaptic marker); (b) the GABA- and taurine-receptive sites (post-synaptic elements); (c) the GABA- and taurine-accumulating activities (uptake processes); and (d) the BDZP receptor activity and the level of the endogenous BDZP-like substance. In addition to the normal conditions, animals with photoreceptor dystrophy or animals treated with taurine-free diet, monosodium glutamate, or iodoacetate-L-malic acid mixture will also be examined.

拟议项目的总体目标是阐明 哺乳动物视网膜中的牛磺酸和γ-氨基丁酸（GABA）。 更多的 具体来说，我们计划进行以下研究： 1. 确定 含 GABA 和牛磺酸的神经元及其过程 通过定位来分析视网膜中这些神经元的突触回路 它们各自的合成酶，即L-谷氨酸 GABA 脱羧酶 (GAD) 和半胱亚磺酸脱羧酶 (CSAD) 使用光和电子显微镜 (EM) 免疫细胞化学检测牛磺酸 分别使用特异性抗 GAD 和抗 CSAD 血清的方法。 2. 到 阐明 GABA 和牛磺酸的功能机制 视网膜受到调节。 其中一种机制是 GABA 的增强作用 苯二氮卓类药物（BDZP）的作用。 因此，精确的细胞和 BDZP受体及其内源性配体的亚细胞分布 视网膜将被确定与特别强调的关系 BDZP 和 GABA 系统之间。 3. 定位牛磺酸和 EM 的 GABA 积累以及牛磺酸和 GABA 接受过程 放射自显影，在体内和体外将视网膜暴露于 放射性标记的 GABA 和牛磺酸及其类似物。 4. 至 确定 GABA 能系统的发育顺序和 含牛磺酸的神经元以及牛磺酸和 GABA 在神经元中的作用 视网膜功能的发育。 将分析以下参数 在不同的发育阶段，例如胚胎阶段、新生儿阶段、 活跃的突触发生和成年，以确定序列 视网膜发育过程中出现的事件：（a）GABA-和 牛磺酸合成活动，即GAD和CSAD活动及其 精确的细胞和亚细胞位置（突触前标记）； （二） GABA 和牛磺酸接受位点（突触后元件）； (c) GABA- 和牛磺酸积累活动（摄取过程）； (d) BDZP 受体活性和内源性 BDZP 样物质的水平。 在 除正常情况外，患有光感受器营养不良或 用不含牛磺酸的饮食、谷氨酸钠或 还将检查碘乙酸盐-L-苹果酸混合物。