Neuronogenesis in the Non-pigmented Retina

非色素视网膜中的神经元发生

• 批准号: 6888016
• 负责人: Richard S Nowakowski
• 金额: $ 31.1万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6888016
• 关键词: albinism; albino mouse; cell cycle; cell proliferation; ganglion cell; neurogenesis; retina; retinal pigment epithelium; visual pigments

DESCRIPTION (provided by applicant): Mammals, including humans, lacking pigment in the retinal pigment epithelial cells have a number of abnormalities of the retina and visual system. Similar abnormalities occur in albinos that lack pigment in the entire body including the eye and in ocular albinos that lack pigment only in the eye. We propose that the lack of pigment affects cell proliferation early in the development of the neural retina and that these abnormalities in cell proliferation affect both cell number and cell class in the adult retina. We describe a hypothetical set of behaviors for the proliferating cells of the retina in pigmented vs non-pigmented eyes and then propose specific experiments to test this hypothesis. For this project mice with two different types of non-pigmented retinas will be used: C57BL/6J-tyrc2J/tyrc2J, which are albino, and Oa1tm1Inc/Y which are ocular albinos. These mice have mutations at different locations in the pigment processing pathway, and both have phenotypes that are substantially similar to their human counterparts. The Oa1tmInc mouse is a murine homolog of human Oa1 (also known as Nettleship-Falls Type Ocular Albinism). The pigmented mice that we will use are chosen to have the same genetic background as the non-pigmented mice. The project has 3 specific aims which will examine at high spatial and temporal resolution: 1) the cell cycle, 2) the proportion of daughter cells leaving vs remaining in the cell cycle, and 3) the generation of cells of specific retinal classes. We will achieve both high spatial and temporal resolution for this project using methods developed in this laboratory that exploit double labeling with two S-phase markers, bromodeoxyuridine and tritiated thymidine. The results obtained will tell us the earliest differences in the production of cells in the developing retina for pigmented and non-pigmented animals including information about regional differences within the retina. Such detailed information is important for understanding how the lack of retinal pigment produces abnormalities and for the rationale development of treatments and therapies.

描述（由申请人提供）：视网膜色素上皮细胞缺乏色素的哺乳动物（包括人类）的视网膜和视觉系统存在许多异常。 类似的异常发生在全身（包括眼睛）缺乏色素的白化病患者和仅眼睛缺乏色素的眼部白化病患者中。 我们认为色素的缺乏会影响神经视网膜发育早期的细胞增殖，并且细胞增殖的这些异常会影响成人视网膜中的细胞数量和细胞类别。 我们描述了色素眼与非色素眼中视网膜增殖细胞的一组假设行为，然后提出具体实验来检验这一假设。 在该项目中，将使用具有两种不同类型的非色素视网膜的小鼠：C57BL/6J-tyrc2J/tyrc2J（白化病）和 Oa1tm1Inc/Y（眼部白化病）。这些小鼠在色素加工途径的不同位置发生突变，并且都具有与人类小鼠基本相似的表型。 Oa1tmInc 小鼠是人类 Oa1 的小鼠同源物（也称为 Nettleship-Falls 型眼白化病）。我们将使用的色素小鼠被选择为与非色素小鼠具有相同的遗传背景。该项目有 3 个具体目标，将以高空间和时间分辨率进行检查：1）细胞周期，2）离开细胞周期的子细胞与保留在细胞周期中的比例，以及 3）特定视网膜类别细胞的生成。 我们将使用本实验室开发的方法实现该项目的高空间和时间分辨率，该方法利用两个 S 期标记物（溴脱氧尿苷和氚化胸苷）的双重标记。 获得的结果将告诉我们色素和非色素动物视网膜发育中细胞生成的最早差异，包括有关视网膜内区域差异的信息。 这些详细信息对于理解视网膜色素缺乏如何产生异常以及治疗和疗法的合理发展非常重要。