Opsin Patterning in Murine Cone Photoreceptors

鼠视锥光感受器中的视蛋白图案

• 批准号: 6778195
• 负责人: MEREDITHE L APPLEBURY
• 金额: $ 37万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-05 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6778195
• 关键词: color visions; cone cell; gene expression; genetic transcription; genetically modified animals; hormone receptor; hormone regulation /control mechanism; immunocytochemistry; immunoprecipitation; in situ hybridization; laboratory mouse; polymerase chain reaction; retinal pigment epithelium; rhodopsin; thyroid hormones; transcription factor; visual photoreceptor; western blottings

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.

描述（由申请人提供）：该申请解决了锥体如何 光感受器在哺乳动物视网膜中被指定以及细胞是如何形成的 组织在视网膜表面。视锥细胞提供主要的 人类视觉的感觉输入。这些细胞赋予其他脊椎动物和我们 通过表达吸收不同颜色的特定视觉色素来实现色觉 光的波长。这些细胞在黄斑变性和其他疾病中的损失 各种形式的视网膜变性是失明的主要原因。长期来看 我们工作的目标是定义程序和分子机制 详细说明视锥细胞的发育及其拓扑结构 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。需要这些信息来设计治疗方法 以防止视锥细胞损失并尝试修复受损的视网膜。 拟议的研究将在小鼠中进行，以利用 细胞被标记或编程的分子遗传学和转基因动物 是经过基因操纵的。该应用程序是基于我们的观察而构建的 小鼠视网膜中的大多数视锥细胞同时表达 S（紫外/蓝色）和 M（绿色）视蛋白， 但不同的时空机制调节这些表达 视蛋白。控制M视蛋白表达并影响M视蛋白表达的因素之一 S 视蛋白的模式是甲状腺核激素受体同种型。小的是 了解视网膜中的甲状腺受体和甲状腺激素。因此，我们 建议（1）指定S和M的时间和空间表达 发育过程中的视蛋白； (2)探讨甲状腺激素的作用 视网膜中的受体； (3) 确定甲状腺受体机制 控制M视蛋白表达； (4)探索控制机制 S视蛋白的空间表达。