VISUAL ADAPTATION IN THE VERTEBRATE RETINA

拟议研究计划的一个主要目标是确定 影响视适应的亚细胞基础 遗传性夜盲视网膜疾病。我们提出的这篇论文 检查表明，这种类型的某些障碍是一种 视觉细胞更新其分子的过程中的异常 成分(E.F.、盘片、突触小泡和其他 膜结合细胞器)，并认为在发病的早期阶段 这种疾病涉及正常细胞骨架结构的破坏， 尤其是微管系统。因此，我们建议研究 用免疫细胞化学和超微结构方法观察细胞的组织 猫视网膜光感受器的微管系统，并测定 三叉神经节对神经元结构和突触传递的影响 微管干扰剂长春新碱。类似的方法将被用于 用动物模型检测视细胞的细胞骨架元素 遗传性视网膜疾病，即夜间失明的阿帕卢萨马，以及 两种患有迟发性进行性视网膜萎缩的狗 (微型贵宾犬和藏梗)。此外，我们还将尝试 确定视紫红质密度和视觉敏感度的变化(以及 这些参数之间的关系)在渐进的不同阶段 影响藏梗的疾病。 因为视网膜电描记术在检测视网膜病变方面发挥了重要作用。 遗传性视网膜广泛存在的视网膜功能障碍 疾病，我们计划对ERG进行成分分析，旨在 提供有关构成综合体的细胞元素的信息 响应的波形。 最后，细胞内研究将在分离的穆勒细胞上进行。 以确定与这些膜特性相关的膜特性 视网膜神经胶质细胞在血管内皮细胞成分生成中的作用 ERG，以及在维持神经元稳定的细胞外环境中 功能。

A major objective of the proposed research program is to identify the subcellular basis of abnormalities that affect visual adaptation in inherited night-blinding retinal disorders. The thesis we propose to examine is that some disorders of this type are manifestations of an aberration in the processes by which the visual cell renews its molecular constituents (e.f., disc lamellae, synaptic vesicles, and other membrane-bound organelles), and that an early stage in the pathogenesis of the disease involves a disruption of the normal cytoskeletal architecture, in particular, the microtubular system. Accordingly, we propose to study with immunocytochemical and ultrastructural methods the organization of the microtubular system in photoreceptors of the cat retina, and to determine the effects on structure and synaptic transmission of the microtubule-disrupting agent, vincristine. Similar methods will be used to examine the cytoskeletal elements of visual cells in animal models of hereditary retinal disorders, namely, the night-blind Appaloosa horse, and two species of dog affected with late-onset progressive retinal atrophy (miniature poodle and Tibetan terrier). In addition, we will attempt to determine changes in rhodopsin density and visual sensitivity (and the relationship between these parameters) at various stages in the progressive disease affecting the Tibetan terrier. Because electroretinography has assumed an important role in detection of the widespread retinal dysfunction associated with hereditary retinal disease, we plan to conduct a component analysis of the ERG designed to provide information on the cellular elements that contribute to the complex waveform of the response. Lastly, intracellular studies are to be performed on isolated Muller cells from the cat retinal to determine those membrane properties that relate to the putative roles of the retinal glia in the generation of components of the ERG, and in maintaining a stable extracellular environment for neuronal function.