DETERMINANTS OF RETINAL PHOTORECEPTOR MORPHOLOGY

视网膜感光器形态的决定因素

• 批准号: 3259561
• 负责人: JOSEPH M CORLESS
• 金额: $ 7.32万
• 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 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3259561
• 关键词: autoradiography; cell membrane; fresh water environment; morphology; retina; rod cell; visual photoreceptor

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.

我们的远程目标是了解影响和 确定脊椎动物感光外部片段的形态 视网膜。 特别是我们问：1）是什么控制了外部直径 细分？ 2）什么控制其形状，以产生类似杆或锥状的形状 结构？ 3）是什么控制了膜关系的拓扑 外部段，以便将光感受体磁盘与 连接到浆膜？ 我们最近对磁盘的形态学研究 青蛙杆外部段（ROS）的边缘揭示了聚集 我们称终端循环（TL）的结构，以强调其 沿磁盘高度弯曲的周围的位置。 TL复合物 似乎由两个相同的半半组成，我们建议这样做 复合物基本上代表了由TL蛋白描述的二聚体 Papermaster等。 当TL复合物的结构特征是 叠加在磁盘开发的几何方案上 Steinberg等人，出现了一个相当简单的假设，可以解释 ROS形态的几个重要特征，即磁盘的对齐 边缘和切口。 此外，它提出了一种通用机制 可能控制磁盘与等离子体的进行性分离 膜，并提供一个简单的解释来说明拓扑 圆锥形和杆外段的磁盘的关系。 反对这一点 背景，我们提出了测试和扩展此假设的实验。 我们的 目的是：1）通过电子显微镜检查A的光感受器 选定的脊椎动物数量以确定TL复合物是否为 如所预测的所有罗斯，并沿着锥形外段呈现 锥盘外围的同源区域。 使用体外视网膜 孵育，检查TL蛋白抗体对盘的影响 边缘形成。 2）进一步定义 围绕大多数外部段的基础的刚性刻板过程。 在 特别是，我们将尝试确定卡因斯卡中的肌动蛋白丝是否是 过程是花纹的，就像在毛细胞的立体中 耳蜗。 我们的基本思想是钙记的过程限制了直径 外部段，并确定切口形成的基本模式 罗斯。 3）确定平均数量和几何特征 TLS之间的连接跨切口，TLS与TL之间的连接 浆膜。 意义：对结构的理解 通常涉及光感受器的关系 可以期望形态可以帮助我们了解广泛的改变 在形态学中涉及多种退化性变化，维生素 缺陷和视网膜的实验操作。