Opsin Patterning in Murine Cone Photoreceptors

描述（由申请人提供）：本申请说明了如何使用圆锥体 光感受器在哺乳动物视网膜中被指定，并且细胞如何 组织在视网膜表面。锥状光感受器提供了 人类视觉的感官输入。这些细胞赋予其他脊椎动物和我们 通过表达特定的视觉色素， 光的波长这些细胞在黄斑变性和其他 视网膜退化是失明的主要原因。长期 我们工作的目标是确定程序和分子机制， 详细说明视锥细胞的发育及其地形组织， 视网膜在定义这些机制时，我们寻求确定内在因素 维持细胞健康。我们需要这些信息来设计治疗方法 以防止视锥细胞丢失并尝试修复受损的视网膜。 将在小鼠中进行拟定的研究，以利用 分子遗传学和转基因动物，其中细胞被标记或编程 都是基因操控的该应用程序是建立在我们的观察， 小鼠视网膜中的大多数视锥共表达S（UV/蓝色）和M（绿色）视蛋白， 但不同的时间和空间机制调节这些表达， 视蛋白控制M视蛋白表达并影响细胞增殖的因素之一是细胞增殖的抑制因子。 视蛋白的模式化是甲状腺核激素受体同种型。之甚少 甲状腺受体和视网膜中的甲状腺激素。因此我们 建议（1）规定S和M的时间和空间表达 探讨甲状腺激素和视蛋白在发育中的作用， 视网膜中的受体;（3）识别甲状腺受体机制， 控制M视蛋白表达;（4）探索控制M视蛋白表达的机制。 视蛋白空间表达。

DESCRIPTION (provided by applicant): This application addresses how cone photoreceptors are specified in the mammalian retina and how the cells are organized across the retinal surface. Cone photoreceptors provide the principal sensory input for human vision. These cells endow other vertebrates and us with color vision by expressing specific visual pigments that absorb different wavelengths of light. The loss of these cells in macular degeneration and other forms of retinal degenerations are major causes of blindness. The long-term objectives of our work are to define the programs and molecular mechanisms that specify the development of cone cells and their topographical organization in the retina. In defining these mechanisms we seek to identify intrinsic factors that maintain the cells in health. This information is needed to devise therapy to prevent cone loss and to attempt repair of the damaged retina. The proposed studies will be carried out in the mouse to take advantage of molecular genetics and transgenic animals in which cells are marked or programs are genetically manipulated. The application is built on our observations that most cones in the mouse retina co-express both S (UV/blue) and M (green) opsin, but different temporal and spatial mechanisms regulate the expression of these opsins. One factor that controls the expression of M opsin and affects the patterning of S opsin is a thyroid nuclear hormone receptor isoform. Little is known about thyroid receptors and thyroid hormone in the retina. Thus, we propose (1) to specify the temporal and spatial expression of the S and M opsins during development; (2) to explore the role of thyroid hormone and receptors in the retina; (3) to identify thyroid receptor mechanisms that control M opsin expression; and (4) to explore mechanisms that control the spatial expression of S opsin.