IDENTIFICATION OF GENES REGULATING RETINAL GANGLION CELL

描述(申请人摘要)：本提案的目的是使用 利用微阵列技术鉴定小鼠基因的表达 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及其丧失是必不可少的 会导致人类的主要眼部疾病。例如，眼内隆起 眼前房内压力可引发细胞凋亡增强 神经节细胞，进而导致青光眼。尽管它们很重要， 然而，视网膜神经节细胞相关基因的知识库 形成和生存是最基本的。利用排列的胚胎视网膜基因 库，此应用程序建议 缺乏关键基因的遗传改变视网膜的基因表达谱 转录因子BRN-3b和Math5。基因靶向研究表明， BRN-3b或Math5导致视网膜神经节细胞的主要缺陷 队形。长期目标是产生全面的基因表达 新生视网膜神经节细胞的形态特征及其遗传学研究 导致视网膜神经节细胞分化的调控机制。这个 具体目标是：(1)建立一个全面的快递数据库 E14.5小鼠视网膜序列；(2)已知基因芯片的制备 视网膜序列用于基因表达模式的分析 开发视网膜；(3)通过比较生成基因表达谱 转基因小鼠品系，以及视网膜发育的不同阶段； 以及(4)制定策略以确定 导致视网膜神经节细胞分化。

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.