DETERMINANTS OF RETINAL PHOTORECEPTOR MORPHOLOGY

视网膜感光器形态的决定因素

• 批准号: 3259563
• 负责人: JOSEPH M CORLESS
• 金额: $ 20.06万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1992-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3259563
• 关键词: cone cell; electron microscopy; morphology; optic disk; rod cell; visual photoreceptor; visual pigments

Our long-range goal is to understand the factors which influence and determine the morphology of photoreceptive outer segments of vertebrate retina. In particular, we ask: 1) What controls the diameter of outer segments? 2) What controls their shape, to yield rod-like or cone-like structures? 3) What controls the topology of membrane relationships in outer segments, so that photoreceptive disks are isolated from or remain connected to the plasmalemma? Our recent morphological studies of the disk margin of frog rod outer segments (ROS) have revealed a clustering of structures we term the terminal loop (TL)-complex, to emphasize their location along the highly curved perimeter of the disk. The TL complex appears to be composed of 2 identical halves, and we suggest that this complex basically represents a dimer of the TL protein described by Papermaster et al. When the structural features of the TL complex are superimposed upon the geometrical scheme of disk development described by Steinberg et al., a rather simple hypothesis emerges which can account for several important features of ROS morphology, namely the alignment of disk margins and incisures. Furthermore, it suggests a general mechanism which probably controls the progressive separation of disks from the plasma membrane, and provides a simple explanation to account for the topological relationships of disks in cone and rod outer segments. Against this background, we propose experiments to test and extend this hypothesis. Our aims are: 1) Examine by electron microscopy the photoreceptors of a selected number of vertebrate species to determine if a TL complex is present in all ROSs as predicted, and in cone outer segments along homologous regions of the cone disk perimeter. Using in vitro retina incubations, examine the effect of antibodies to the TL protein on disk margin formation. 2) Further define the structure and function of the rigid calycal processes which surround the base of most outer segments. In particular, we will try to determine if the actin filaments within calycal processes are festooned, as in the stereocilia of hair cells in the cochlea. Our basic idea is that the calycal processes limit the diameter of outer segments and determine the basic pattern of incisure formation in ROSs. 3) Determine the average number and geometrical features of connections between TLs across incisures, and between TLs and the plasmalemma. Significance: An understanding of the structural relationships normally involved in the maintenance of photoreceptor morphology can be expected to help us understand the extensive alterations in morphology involved in a wide range of degenerative changes, vitamin deficiences, and experimental manipulations of the retina.

我们的长期目标是了解影响和影响的因素 确定脊椎动物感光外节的形态 视网膜。 我们特别要问：1）什么控制外径 细分？ 2）什么控制它们的形状，产生棒状或圆锥状 结构？ 3）什么控制着膜关系的拓扑结构 外部部分，以便感光盘与外部部分隔离或保留 与质膜有关？ 我们最近对圆盘的形态学研究 青蛙杆外节（ROS）的边缘揭示了一组 我们将这种结构称为末端环（TL）复合体，以强调它们的 沿着盘的高度弯曲的周边的位置。 TL复合体 似乎由两个相同的半部分组成，我们建议这个 复合物基本上代表了 TL 蛋白的二聚体，描述为 帕帕马斯特等人。 当TL复合体的结构特征为 叠加在磁盘发展的几何方案上，描述为 Steinberg 等人提出了一个相当简单的假设，可以解释 ROS形态的几个重要特征，即圆盘的排列 边缘和切口。 此外，它还提出了一种通用机制 可能控制圆盘与等离子体的逐渐分离 膜，并提供了一个简单的解释来解释拓扑 锥体和杆外段中圆盘的关系。 反对这个 背景下，我们提出实验来检验和扩展这一假设。 我们的 目的是： 1）通过电子显微镜检查光感受器 选择一定数量的脊椎动物来确定 TL 复合物是否是 正如预测的那样，存在于所有 ROS 中，并且存在于沿着 锥盘周长的同源区域。 使用体外视网膜 孵育，检查抗体对磁盘上 TL 蛋白的影响 边际形成。 2）进一步定义了结构和功能 围绕大多数外节基部的刚性花萼突起。 在 特别是，我们将尝试确定肾盏内的肌动蛋白丝是否 突起是装饰性的，就像毛细胞的静纤毛一样 耳蜗。 我们的基本想法是肾盏突限制了直径 外部节段并确定切痕形成的基本模式 ROS。 3) 确定平均数量和几何特征 跨切口的 TL 之间以及 TL 与 质膜。 意义：对结构的理解 通常涉及光感受器维持的关系 形态学有望帮助我们理解广泛的变化 在涉及广泛退行性变化的形态学中，维生素 缺陷和视网膜的实验操作。