MOLECULAR GENETICS OF OPEN ANGLE GLAUCOMA

青光眼是一组异质性的疾病，它们共同构成了美国人失明的第二大原因，也是非洲裔美国人失明的主要原因。然而，人们对这种疾病的潜在基础知之甚少。青光眼最常见的形式，被称为原发性开角型青光眼，发生在眼睛解剖结构正常的情况下。我们研究的长期目标是了解导致开角型青光眼的机制。我们最近发现了一种基因LMX1B的突变，这种突变会导致一种发育综合征，即胫髌骨综合征（NPS），其中包括开角型青光眼。LMX1B基因编码一种具有转录因子特征的蛋白质，这种蛋白质可以开启或关闭其他基因。当前提案的主要目标是通过鉴定由LMX1B调控的基因和与之一起工作的蛋白质辅助因子，将LMX1B基因置于产生和维持正常眼睛的遗传调控途径的背景下。我们还将研究LMX1B或受其调控的基因是否在原发性开角型青光眼患者的DNA中发生突变，并可能在美国发现导致该疾病的新基因，最终导致更好的诊断和治疗。

Glaucoma i a heterogeneous group of diseases which together constitute the second leading cause of blindness among Americans, and the leading cause among African Americans. Yet, little is known about the underlying basis of the disorder. The most common form of glaucoma, known as primary open angle glaucoma, occurs in a setting in which the anatomical structures of the eye appear normal. The long term goal of our research is to understand the mechanisms responsible for causing open angle glaucoma. We have recently identified mutations in a gene, LMX1B, which cause a developmental syndrome known as mail-patella syndrome (NPS) that includes open angle glaucoma as a feature. The LMX1B gene encodes a protein with characteristics of a transcription factor, a protein that turns other genes on or off. A primary goal of the current proposal is to place the LMX1B gene in the context of the genetic regulatory pathways which produce and maintain the normal eye, through identification of gene regulated by LMX1B and protein cofactors which work with it. We will also investigate whether LMX1B, or genes regulated by it, are mutated in the DNA of people with primary open angle glaucoma and may identify new genes responsible for the disease in Americans, ultimately leading to better diagnosis and treatment.