VISUAL ADAPTATION IN THE VERTEBRATE RETINA

拟议研究计划的一个主要目标是确定 亚细胞基础的异常，影响视觉适应， 遗传性夜盲视网膜疾病 我们提出的论文 检查的是，这种类型的一些疾病是一种 视觉细胞更新其分子的过程中的畸变 成分（例如，椎间盘板、突触囊泡和其他 膜结合的细胞器），并在发病的早期阶段， 该疾病涉及正常细胞骨架结构的破坏， 特别是微管系统。 因此，我们建议研究 用免疫细胞化学和超微结构的方法， 微管系统的光感受器的猫视网膜，并确定 对结构和突触传递的影响， 微管破坏剂长春新碱 类似的方法将用于 在动物模型中检查视觉细胞的细胞骨架元素， 遗传性视网膜疾病，即夜盲阿帕卢萨马， 两种患迟发性进行性视网膜萎缩的狗 （迷你贵宾犬和西藏梗）。 此外，我们将努力 确定视紫红质密度和视觉灵敏度的变化（以及 这些参数之间的关系）在各个阶段的进展 一种影响西藏梗的疾病。 由于视网膜电图在检测视网膜病变中起着重要的作用， 与遗传性视网膜病变相关的广泛的视网膜功能障碍 疾病，我们计划进行ERG的成分分析， 提供有关构成复合体的细胞成分的信息 响应的波形。 最后，对分离的Muller细胞进行细胞内研究 从猫的视网膜中，来确定那些与 视网膜神经胶质细胞在视网膜神经元生成中的作用 视网膜电图，并在维持稳定的细胞外环境，为神经元 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.