VISUAL ADAPTATION IN THE VERTEBRATE RETINA

描述（研究者摘要）：拟定研究的主要目的 一项研究计划是确定异常的亚细胞起源 影响光感受器的结构和功能完整性 遗传性夜盲症 与此相关的缺陷 疾病的类型变化很大。 在某些固定条件下， 异常似乎仅限于细胞的适应机制;在 进行性疾病，视觉细胞的结构架构是 受影响，一个恶化的过程开始，最终 涉及整个神经视网膜 在此期间进行的实验 这一补助期的目的是测试各种假设有关 这些异常的分子基础，以及 被它们的表达所干扰的适应过程。 比如说， 从受体到二级神经元的神经传递似乎是 在某些形式的静止性夜盲症中严重减弱。 的作用 的微管系统在维持功能的能力， 细胞的突触末端将在实验中确定， 视细胞的微管被破坏， 从合成位点到突触末端的蛋白质被追踪 放射自显影。 其他细胞骨架元件（例如，血影蛋白和 几种膜相关蛋白）被认为参与了 受体外节的盘膜有序排列。 这些蛋白质将被生化和免疫细胞化学研究， 西藏梗患有进行性视网膜萎缩， 其特征是在其早期阶段的迷失方向和脱离的 双层花盘 此外，自适应过程的基本特征将 在IRBP在类维生素A穿梭于 光感受器和色素上皮，以及在其他实验中， 脊椎动物视杆细胞的光诱导脱敏。 最后，实验 在放射状胶质细胞（Muller细胞）和水平细胞上进行， 越来越多的人意识到视觉功能依赖于 这些细胞的组织和膜特性，以及它们各自的 在调节视网膜中的递质作用中的作用。 后者 在神经毒性方面具有广泛的影响， 到神经元-神经胶质细胞的相互作用， 信号和视觉信息的处理。

DESCRIPTION (investigator's abstract): The major objective of the proposed research program is to identify the subcellular origins of abnormalities that affect the structural and functional integrity of the photoreceptors in inherited night-blinding disorders. The defects associated with these types of disorder vary widely. In some stationary conditions, the abnormality appears to be confined to the cell's adaptive mechanism; in the progressive diseases, the structural architecture of the visual cell is affected, and a process of deterioration is set into motion that eventually involves the entire neural retina. The experiments to be conducted during this grant period are designed to test various hypotheses concerning the molecular bases of these abnormalities, as well as the basic features of the adaptive process that is perturbed by their expression. For example, neurotransmission from receptors to second-order neurons appears to be grossly attenuated in some forms of stationary night blindness. The role of the microtubular system in maintaining the functional competence of the cell's synaptic terminal will be determined in experiments in which the microtubules of the visual cells are disrupted, and the movement of proteins from sites of synthesis to the synaptic terminal is tracked autoradiographically. Other cytoskeletal elements (e.g., spectrin and several membrane-associated proteins) are thought to be involved in the ordered alignment of the disc membranes of the receptor outer segment. These proteins will be studied biochemically and immunocytochemically in Tibetan terriers affected with progressive retinal atrophy, a disease characterized in its early stages by disorientation and detachment of the bilamellar discs. In addition, basic features of the adaptive process will be examined in studies on the role of IRBP in shuttling retinoids between photoreceptors and the pigment epithelium, and in other experiments on the light-induced desensitization of vertebrate rods. Lastly, experiments to be performed on the radial glia (Muller cells) and horizontal cells reflect a growing awareness of the dependence of visual function on the organization and membrane properties of these cells, and their respective roles in the regulation of transmitter action in the retina. The latter has wide-ranging implications with regard to neurotoxicity, and in relation to neuron-glia interactions, the intercellular transfer of electrical signals, and the processing of visual information.