MOLECULAR GENETICS OF OPEN ANGLE GLAUCOMA

青光眼是一组异质性疾病，其共同构成美国人失明的第二大原因，并且是非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。青光眼的最常见形式，称为原发性开角型青光眼，发生在眼睛的解剖结构看起来正常的情况下。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LMX 1B的突变，这种突变会导致一种发育综合征，称为mail-patella综合征（mail-patella syndrome），其中包括开角型青光眼。LMX 1B基因编码一种具有转录因子特征的蛋白质，这种蛋白质可以打开或关闭其他基因。目前建议的一个主要目标是通过鉴定LMX 1B调控的基因和与其一起工作的蛋白质辅因子，将LMX 1B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LMX 1B或其调控的基因，在原发性开角型青光眼患者的DNA中发生突变，并可能在美国人中识别出导致这种疾病的新基因，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.