ROD OUTER SEGMENTS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 目标是获得感光细胞及其内部的三维图像 来自野生型视网膜和来自突变对应于 人类视网膜疾病。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和疾病的结构相关性 发病机制。最有趣的结构将是扁平的盘膜 填满感光细胞外节的膜袋。这些都塞满了 高密度的视紫红质和这些膜中视紫质的组织是一个主题 有相当大的争议。在许多情况下观察到这些膜的解体 人类视网膜变性的小鼠模型。我们希望看到的是 这些膜及其与细胞骨架元素和血浆的连接 薄膜。以前只在切片的样本中观察到了这些 和负染，或经受冷冻蚀刻程序。低温电子层析成像 提供了在完整的细胞中观察这些的机会(至少在细胞的边缘) 除了快速冷冻，没有其他操作。同样令人感兴趣的是连接 纤毛，连接内外节段的一束微管，用于 将外部管段部件运送到其适当位置。基因缺陷涉及到的 这种纤毛的结构和功能以及跨纤毛的运输也导致视网膜 退化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 cytoskeletal 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.