FACTORS DETERMINING INTRAOCULAR PRESSURE

青光眼是导致失明的主要原因。 它涉及死亡的 视网膜神经节细胞和视神经变性。 高 眼内压（IOP）经常与青光眼有关。 是 被认为是一个重要的致病因素。 多重因素 与眼内压相互作用造成损害的定义尚不明确。 私家侦探很长 术语目标是鉴定和表征 导致IOP升高和青光眼。 最近的进展使 青光眼相关染色体区域的鉴定更实用 比以往任何时候都多 确定特定致病基因的任务， 然而，要证明它们的相关性仍然很困难。 使用 小鼠作为动物模型，PI将利用改变 内源性基因，以测试其对IOP调节的功能意义 和青光眼。 为了开始这一过程，研究人员开发了一个 可靠的方法来测量小鼠的IOP。 PI建议使用转基因小鼠来评估 用于IOP调节的利钠肽系统。 利钠肽 (NPs)在调节体液量和移动液体方面很重要， 隔舱之间。 NPs及其受体（NPR）存在于 眼睛 它们发生在产生眼液的睫状上皮中 （房水）和房水引流（流出）的细胞中 通路 现有证据表明，NP可降低IOP。 在 这种影响的至少一部分似乎是由于NP刺激的增加， 房水流出 因此，NP或NPR的遗传缺陷可能导致 IOP升高，可能是导致 眼压升高和青光眼 为了支持这一点，初步研究表明， 纯合突变的小鼠， 心房利钠肽和脑利钠肽都具有 IOP显著升高。 为了确定这种突变 改变眼压，并确定遗传缺陷的后果， 利钠肽系统的其他组分，PI建议检测： 1. 如果心房钠尿肽（ANP）和脑 利钠肽（BNP）可引起IOP升高。 2. 如果基因 利钠肽受体1（NPR 1）的缺乏可引起IOP升高。 3. 如果C型利钠肽（CNP）的遗传缺陷可导致 IOP升高。 这些研究应该确定这些NP系统基因是否 合理的候选人有助于人类青光眼。 他们很可能 增加对各种利钠肽作用的了解， 利钠肽受体在IOP稳态中的作用

DESCRIPTION: Glaucoma is a major cause of blindness. It involves death of retinal ganglion cells and degeneration of the optic nerve. High intraocular pressure (IOP) is frequently associated with glaucoma. It is thought to be an important causative factor. The multiple factors interacting with IOP to cause damage are not clearly defined. The PI's long term objective is to identify and characterize genetic factors that contribute to elevated IOP and glaucoma. Recent advances make the identification of chromosomal regions involved in glaucoma more practical than ever before. The task of identifying the specific causative genes in humans and of proving their relevance, however, remains difficult. using mice as an animal model, the PI will take advantage of the ability to alter endogenous genes to test their functional significance for IOP regulation and glaucoma. To start this process the investigator has developed a reliable method to measure IOP in mice. The PI proposes to use genetically altered mice to assess the importance of the natriuretic peptide system for IOP regulation. The natriuretic peptides (NPs) are important in regulating body fluid volume, and in moving fluid between compartments. The NPs and their receptors (NPRs) are present in the eye. They occur in the ciliary epithelium that produces the ocular fluid (aqueous humor) and in cells of the aqueous humor drainage (outflow) pathway. Available evidence suggests that the NPs act to decrease IOP. At least part of this effect seems to result from NP-stimulated increases in aqueous outflow. A genetic deficiency of NPs or NPRs, thus, may result in increased IOP and could be one of the multiple facotrs contributing to elevated IOP and glaucoma. In support of this, preliminary studies suggest that mice that are homozygous for a mutation that diminishes production of both atrial natriuretic peptide and brain natriuretic peptide have significantly increased IOP. To determine the extent to which this mutation alters IOP, and to determine the consequences of genetic deficiencies in other components of the natriuretic peptide system, the PI proposes to test: 1. If a genetic deficiency of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) can cause increased IOP. 2. If a genetic deficiency of natriuretic peptide receptor 1 (NPR1) can cause increased IOP. 3. If a genetic deficiency of C-type natriuretic peptide (CNP) can cause increased IOP. These studies should determine if these NP system genes are reasonable candidates to contribute to human glaucoma. They are likely to increase understanding of the roles of various natriuretic peptides and natriuretic peptide receptors in IOP homeostasis.