FACTORS DETERMINING INTRAOCULAR PRESSURE

描述：青光眼是导致失明的主要原因。它涉及到死亡的 视网膜神经节细胞和视神经变性。高 眼压(IOP)经常与青光眼有关。它是 被认为是一个重要的致病因素。多重因素 与眼压相互作用造成损害的定义并不明确。圆周率长 术语目标是识别和表征遗传因素 会导致眼压升高和青光眼。最新的进展使 识别与青光眼有关的染色体区域更实用 比以往任何时候都要好。识别特定的致病基因的任务 然而，要证明人类及其相关性仍然是困难的。使用 以小白鼠为动物模型，会利用小白鼠的能力改变 检测内源性基因对眼压调节的功能意义 还有青光眼。为了开始这一过程，调查人员开发了一种 测定小鼠眼压的可靠方法。 PI建议使用转基因小鼠来评估 调节眼压的利钠肽系统。利钠肽 (NP)在调节体液容量和运动液体中起重要作用 在车厢之间。NPs及其受体(NPR)存在于 眼睛。它们出现在产生眼液的睫状体上皮细胞中。 (房水)和房水引流的细胞(流出) 路径。现有证据表明，NPs具有降低眼压的作用。在… 这种影响的最小部分似乎是由NP刺激的 房水流出。因此，NPs或NPR的遗传缺陷可能会导致 眼压升高，可能是导致眼压升高的多种因素之一 眼压升高和青光眼。为了支持这一点，初步研究表明 是纯合突变的小鼠，这种突变减少了 心钠素和脑利钠肽都有 眼压显著升高。以确定这种突变的程度 改变眼压，并确定遗传缺陷的后果 对于利钠肽系统的其他组件，PI建议测试： 1.如果心钠素(ANP)和脑的遗传性缺陷 钠尿肽(BNP)可引起眼压升高。2.如果一个基因 钠尿肽受体1(NPR1)缺乏会导致眼压升高。 3.如果C型利钠肽(CNP)的遗传缺陷可导致 眼压升高。这些研究应该确定这些NP系统基因是否 合理的候选人会导致人类青光眼。他们很可能会 增加对各种利钠肽作用的了解，并 钠尿肽受体在眼压动态平衡中的作用

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.