CHARACTERIZATION OF GENES IN NORMAL AND AMD RETINAS

描述(申请人提供)：黄斑是一种独特的高度 灵长类动物视网膜的特化区域。它含有最高密度的 视杆细胞和视锥感光细胞，包围视锥中心凹，视锥中心凹 调节高敏锐度的中心视力。不幸的是，中心视力的丧失是一种 各种视网膜变性的显著后果，包括视锥视杆细胞 营养不良和黄斑变性。例如，与年龄相关的视力丧失 黄斑变性(AMD)约占所有注册病例的一半 西方世界的失明。这些退化的特征是 视杆细胞和视锥细胞的功能障碍和最终死亡 黄斑内覆盖视网膜色素上皮(RPE)细胞。上一首 研究表明，视乳头周围视杆感光细胞的丧失先于 然而，我们对黄斑和黄斑中心凹机制的理解 这一过程中锥体损失较小。看起来圆锥体，尤其是中心凹 视锥细胞，在视网膜的一个区域有生存的能力 退化的倾向。为了了解黄斑和黄斑的功能作用 黄斑中心凹视锥细胞在正常视网膜内稳态和视网膜病变生物学中的作用 病变的视网膜，我们认为定义分子是至关重要的 这些细胞的“指纹”。我们假设差异基因表达 黄斑中心凹视锥定义了黄斑独特的微环境，包括 中心凹。此外，其中一些基因可能与疾病有关。 敏感性，而其他的可能提高感光细胞的存活。因此， 提出了以下目标：(1)寻找在细胞中优先表达的基因 灵长类中心凹。(2)鉴定中心凹相关/视锥特异性基因和 确定它们所编码的蛋白质。(三)明确职能定位 中心凹相关蛋白。我们研究计划的中心主题是 灵长类动物视网膜中央毫米的差异基因表达(in 黄斑中心凹视锥感光细胞)对黄斑变性的病理影响。 了解正常的中心凹视锥生物学及其在疾病意志中的变化 为延长光感受器存活时间的治疗提供理论依据 黄斑变性。

DESCRIPTION (provided by applicant): The macula is a unique and highly specialized region of the primate retina. It contains the highest densities of rod and cone photoreceptor cells and encompasses the cone-enriched fovea, which mediates high acuity central vision. Unfortunately, loss of central vision is a significant consequence of various retinal degenerations, including cone-rod dystrophies and macular degenerations. For example, vision loss in age-related macular degeneration (AMD), is responsible for about one-half of all registered blindness in the Western world. These degenerations are characterized by dysfunction and, ultimately, death of rod and cone photoreceptors and the overlying retinal pigment epithelial (RPE) cells in the macula. Previous studies have suggested that perifoveal rod photoreceptor loss precedes that of cones in AMD; however, our understanding of the mechanism of macular and foveal cone loss in this process is poor. It appears that cones, especially foveal cones, have a capacity for survival in a region of the retina that has a propensity for degeneration. To understand the functional role of macular and foveal cones in the homeostasis of the normal retina and in the pathobiology of the diseased retina, we believe that it is critical to define the molecular "fingerprint" of these cells. We hypothesize that differential gene expression by foveal cones defines the unique microenvironment of the macula, including the fovea. Furthermore, some of these genes may contribute to disease susceptibility while others may enhance photoreceptor survival. Thus, the following aims are proposed: (1) Identify genes preferentially expressed in the primate fovea. (2) Characterize fovea-associated/cone-specific genes and identify the proteins they encode. (3) Determine the functional roles of fovea-associated proteins. The central theme of our research program is that differential gene expression in the central millimeter of primate retina (in foveal cone photoreceptors) impacts on the pathology of macular degenerations. Understanding normal foveal cone biology and its alteration in disease will provide the rationale for therapies to prolong photoreceptor survival in macular degeneration.