Neuronogenesis in the Non-pigmented Retina

非色素视网膜中的神经元发生

基本信息

批准号：
7415015
负责人：
Richard S Nowakowski
金额：
$ 29.6万
依托单位：
UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-05-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7415015
关键词：
2&apos -Deoxythymidine Accounting Adult Affect Age Albinism Algorithms Animals Appearance Area Axon Behavior Books Bromodeoxyuridine Caliber Cell Count Cell Cycle Cell Death Cell Proliferation Cells Class Competence Data Date/Time Defect Development Developmental Process Dorsal Embryo Embryonic Development Epithelial Event Eye Generations Genetic Goals Growth Hereditary Disease Homologous Gene Human Label Laboratories Lateral Left Length Link Location Mammals Measures Medial Methods Modeling Mus Mutation Neocortex Neural Retina Neurons Nose Numbers Ocular Albinism Output Paper Pathway interactions Pattern Peripheral Phase Phenotype Photoreceptors Pigment Epithelium Pigmentation physiologic function Pigments Population Principal Investigator Process Production Proliferating Relative (related person)Reporting Research Personnel Resolution Retina Retinal Retinal Pigments Rice Route Sorting - Cell Movement Staging Structure Structure of retinal pigment epithelium Surface Testing Thymidine Time Variant Visual system structure Work Writing base cell type concept daughter cell day ganglion cell neocortical postnatal programs regional difference research study retinal rods size therapy development type I Ocular albinism

项目摘要

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）：包括人类在内的哺乳动物，在视网膜色素上皮细胞中缺乏色素具有视网膜和视觉系统的多种异常。白化病在整个体内缺乏色素的白化病中发生了类似的异常，包括眼睛和仅在眼睛中缺乏色素的眼睛白化病。我们建议缺乏色素会影响神经视网膜发展的早期细胞的增殖，并且细胞增殖的这些异常会影响成年视网膜的细胞数和细胞类别。我们描述了在有色眼睛与非色素的眼睛中视网膜增殖细胞增殖细胞的假设行为，然后提出了特定的实验来检验该假设。对于该项目，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，是白化病，而OA1TM1INC/Y是Ocular Albinos。这些小鼠在色素加工途径的不同位置有突变，并且两者的表型与人类对应物基本相似。 OA1TMINC小鼠是人oa1的鼠同源物（也称为净造成眼睛型眼睛白化病）。选择我们将使用的色素小鼠具有与非色素小鼠相同的遗传背景。该项目具有3个特定目的，这些目标将以高空间和时间分辨率检查：1）细胞周期，2）留在细胞周期中剩余的子细胞的比例； 3）特定视网膜类别的细胞产生。我们将使用该实验室中开发的方法来实现该项目的高空间和时间分辨率，该方法用两个S相标记物（Bromodoxyuridine and Tridity胸苷）利用双重标记。获得的结果将告诉我们，用于色素和非色调动物的开发视网膜中细胞产生的最早差异，包括有关视网膜内区域差异的信息。这样的详细信息对于理解缺乏视网膜色素如何产生异常以及治疗和疗法的基本发展很重要。