ROD OUTER SEGMENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 其目标是从野生型视网膜和具有与人类视网膜疾病相对应的突变的小鼠视网膜获得感光细胞及其内部结构的三维图像。了解这些结构将有助于我们理解健康光感受器的正常结构，以及疾病发病机制的结构相关性。最有趣的结构将是盘状膜，即填充光感受器外部节段的扁平的膜袋。这些膜中含有高密度的视紫红质，这些膜中视紫红质的组织是一个相当有争议的主题。在许多人类视网膜变性的小鼠模型中观察到这些膜的解体。我们希望看到这些膜的结构组织以及它们与细胞骨架元素和质膜的联系。以前只在切片和负染的样品中观察到这些，或者在冷冻蚀刻过程中观察到。冷冻电子断层扫描提供了在完整的细胞中观察这些细胞的机会(至少在细胞的边缘)，除了快速冷冻外，不需要任何操作。连接纤毛也是有趣的，它是一束微管，连接内、外节段，用于将外节成分输送到合适的位置。涉及纤毛结构和功能以及跨纤毛运输的基因缺陷也会导致视网膜退化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal is to obtain three-dimensional images of photoreceptor cells and their internal structures from wildtype retinas and from retinas of mice with mutations corresponding to human retinal disease. Understanding these structures will help us to understand the normal structure of healthy photoreceptors, and the structural correlates of disease pathogenesis. The most interesting structures will be the disk membranes, flattened membrane sacks which fill up the photoreceptor outer segments. These are packed with rhodopsin at high density and the organization of rhodopsin in these membranes is a subject of considerable controversy. Disorganization of these membranes is observed in a number of mouse models of human retinal degeneration. We hope to see the structural organization of these membranes and their connections to cytokeletal elements and the plasma membrane. These have been previously observed only in samples that have been sectioned and negatively stained, or subjected to freeze-etch procedures. Cryo-electron tomography offers the opportunity to observe these in intact cells (at least on the margins of the cell) with no manipulations other than rapid freezing. Also of interest will be the connecting cilium, a bundle of microtubules that connects the inner and outer segments and serves to transport outer segment components to their proper location. Defects in genes involved in the structure and function of this cilium and the trans-cilium transport also lead to retinal degeneration.