Opsin Patterning in Murine Cone Photoreceptors

描述(由申请人提供)：本申请说明如何使用圆锥体 哺乳动物视网膜中的光感受器是特定的，细胞是如何 在视网膜表面组织起来的。视锥感光器提供了主要的 人类视觉的感官输入。这些细胞赋予了其他脊椎动物和我们 通过表达特定的视觉色素来吸收不同的颜色 光的波长。黄斑变性和其他疾病中这些细胞的丢失 各种形式的视网膜退化是导致失明的主要原因。长期的 我们工作的目标是定义程序和分子机制， 说明锥体细胞的发育及其地形组织 视网膜。在定义这些机制时，我们试图确定内在因素 来维持细胞的健康。这些信息是设计治疗方法所必需的 以防止视锥细胞丢失，并尝试修复受损的视网膜。 建议的研究将在老鼠身上进行，以利用 分子遗传学和对细胞进行标记或编程的转基因动物 都是被基因操纵的。这个应用程序建立在我们的观察基础上 小鼠视网膜中的大多数视锥细胞同时表达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基因的表达 奥辛斯。控制M视蛋白表达的一个因素，并影响 S视蛋白是一种甲状腺核激素受体亚型。小才是 已知视网膜中的甲状腺受体和甲状腺激素。因此，我们 建议(1)明确S和M的时空表达 (2)探讨甲状腺激素在发育过程中的作用； 视网膜中的受体；(3)识别甲状腺受体的机制 控制M-opsin的表达；以及(4)探索控制M-opsin表达的机制 S视点的空间表达。

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.