VISUAL ADAPTATION IN THE VERTEBRATE RETINA

说明(调查员摘要)：建议的主要目标 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的完整性 患有遗传性夜盲症。与这些相关的缺陷 精神障碍的类型千差万别。在某些静止条件下， 异常似乎局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 受到影响，并开始一个恶化的过程，最终 牵涉到整个神经视网膜。将在以下时间进行的实验 这一授权期旨在测试关于 这些异常的分子基础以及这些异常的基本特征 被他们的表情所扰乱的适应过程。例如, 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中严重减弱。角色 微管系统在维持机体功能能力中的作用 细胞的突触终末将在实验中确定 视觉细胞的微管被破坏，视神经的运动 追踪从合成部位到突触末端的蛋白质 放射自显影。其他细胞骨架元素(例如，血影蛋白和 几种膜相关蛋白)被认为参与了 受体外段的盘膜排列整齐。 将对这些蛋白质进行生物化学和免疫细胞化学研究。 藏梗患有进行性视网膜萎缩，这是一种疾病 以其早期阶段为特征的是迷失方向和脱离 双板层间盘。此外，适应进程的基本特征将 在关于IRBP在维甲酸类化合物之间穿梭的作用的研究中得到检验 光感受器和色素上皮，以及在其他关于 脊椎动物杆状物的光诱导脱敏。最后，实验证明 对放射状胶质细胞(Muller细胞)和水平细胞进行反射 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 在调节视网膜递质活动中的作用。后者 对神经毒性有广泛的影响，并与 对于神经元-神经胶质细胞之间的相互作用，细胞间的电传递 信号，以及视觉信息的处理。

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.