IDENTIFICATION OF GENES REGULATING RETINAL GANGLION CELL

描述（申请人摘要）：本提案的目的是使用 微阵列技术，以确定小鼠的基因，其产品涉及 视网膜神经节细胞的分化、维持和存活。 视网膜神经节细胞对正常视力和视力丧失至关重要 会导致人类的主要眼病。例如，眼内升高 眼睛前房内的压力可以触发增强的细胞凋亡 神经节细胞中，这反过来又导致青光眼。尽管它们很重要， 然而，与视网膜神经节细胞相关的基因的知识基础 形成和生存是基本的。使用排列的胚胎视网膜cDNA 最近建成的图书馆，本申请提出， 基因改变视网膜的基因表达模式缺乏关键 转录因子Brn-3b和Math 5。基因靶向研究表明， Brn-3b或Math 5导致视网膜神经节细胞的主要缺陷 阵长期目标是产生全面的基因表达 新形成的视网膜神经节细胞的特征，并确定遗传 导致视网膜神经节细胞分化的调节机制。的 具体目标是：（1）建立一个全面的表达数据库 来自E14.5小鼠视网膜的视网膜序列;（2）用已知的 视网膜序列，用于在基因表达谱中的应用 视网膜发育;（3）通过比较产生基因表达谱 基因改变的小鼠品系和视网膜发育的不同阶段; 和（4）制定战略，以确定遗传调控网络， 导致视网膜神经节细胞的分化。

DESCRIPTION (Applicant's abstract): The objective of this proposal is to use microarray technology to identify mouse genes whose products are involved in the differentiation, maintenance, and survival of retinal ganglion cells. Retinal ganglion cells are essential for normal vision and their loss contributes to major eye diseases in humans. For example, elevated intraocular pressure within the anterior chamber of the eye can trigger enhanced apoptosis in ganglion cells, which in turn leads to glaucoma. Despite their importance, however, the knowledge base of genes associated with retinal ganglion cell formation and survival is rudimentary. Using an arrayed embryonic retinal cDNA library that has recently been constructed, this application proposes to profile gene expression patterns in genetically altered retinas lacking the key transcription factors Brn-3b and Math5. Gene targeting has shown that loss of either Brn-3b or Math5 leads to major defects in retinal ganglion cell formation. The long-term goal is to generate comprehensive gene expression profiles for newly forming retinal ganglion cells and to determine the genetic regulatory mechanisms that lead to retinal ganglion cell differentiation. The specific aims are to: (1) Establish a comprehensive database of expressed retinal sequences from E14.5 mouse retina; (2) Prepare gene chips with known retinal sequences for use in profiling patterns of gene expression in the developing retina; (3) Generate gene expression profiles by comparing genetically altered mouse lines, and different stages of retinal development; and (4) Develop strategies to determine the genetic regulatory networks that lead to the differentiation of retinal ganglion cells.