SELENIUM-INDUCED GLAUCOMA

硒诱发的青光眼

• 批准号: 6986093
• 负责人: W Daniel Stamer
• 金额: $ 14.7万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6986093
• 关键词: apoptosis; cell biology; cell growth regulation; chemical structure function; clinical research; cytotoxicity; dietary supplements; estradiol; extracellular matrix; eye; glaucoma; hormone regulation /control mechanism; human tissue; intraocular aqueous flow; intraocular pressure; metalloendopeptidases; nutrition related tag; organ culture; selenium; tissue /cell culture; trabecular meshwork

DESCRIPTION (provided by applicant): Glaucoma, the second leading cause of irreversible blindness in the United States, is a group of disorders characterized by a progressive loss of retinal ganglion cells with associated loss of vision that is in most cases coincident with elevated intraocular pressure (IOP). Today and in the foreseeable future, those with glaucoma are clinically managed with pharmaceutical agents that lower IOP. Elevated IOP in those with glaucoma results from defective regulatory processes in the outflow pathway. Consequently, a current area of focus for glaucoma research and a program priority area for the National Eye Institute (Glaucoma Panel Program Objective #3) is to understand the molecular and cellular mechanisms that underlie the regulation of fluid flow through the human outflow pathway. During a recent safety review in a current selenium-supplementation intervention trial (the Nutritional Prevention of Cancer Trial) an increased incidence of primary open-angle glaucoma amongst participants, particularly women, in the selenium treatment group was uncovered. In the present proposal, we examine the effects of selenium on the biology of human trabecular meshwork cells and outflow function both in the presence and absence of 17 beta-estradiol. Hypothesized effects of selenium on outflow function are consistent with demonstrated effects of selenium on other cell types that include alterations in extracellular matrix turnover, cell cycle arrest and induction of apoptosis. The present study will examine these endpoints in cell and organ culture models and thus is innovative for at least two reasons: First, determination of selenium effects on cell biology in human outflow pathway will provide insight into and/or support for critical regulatory mechanisms that control outflow facility. Second, selenium treatment of outflow tissues may provide a novel glaucoma model to study changes in the outflow pathways at the molecular and cellular level in a controlled manner. If successful, results obtained from these investigations will provide a basic understanding of selenium effects on aqueous outflow facility, uncover novel therapeutic targets for glaucoma treatment and generate a foundation for future investigations.

描述（由申请人提供）：青光眼是美国不可逆失明的第二主要原因，是一组疾病，其特征是视网膜神经节细胞逐渐丧失，视力丧失与眼内压（IOP）相关的视力丧失。今天和可预见的将来，青光眼的人在临床上使用降低IOP的药物管理。在流出途径中有缺陷的调节过程导致青光眼的IOP升高。因此，目前用于青光眼研究的重点领域和国家眼科研究所的计划优先区域（青光眼图案目标＃3）是了解基于通过人类流出途径调节流体流动的分子和细胞机制。 在当前一项硒支持干预试验（癌症试验的营养预防试验）中最近的安全性审查中，发现了硒治疗组中参与者（尤其是妇女）原发性开态青光眼的发生率增加。在本提案中，我们检查了硒对人小梁网细胞生物学的影响以及在存在和不存在17个β-雌二醇的情况下流出功能。硒对流出功能的假设影响与硒对其他细胞类型的影响一致，包括细胞外基质转换，细胞周期停滞和诱导凋亡的改变。本研究将检查细胞和器官培养模型中的这些终点，因此至少有两个原因是创新的：首先，确定硒对人流出途径中细胞生物学的影响将为控制流出设施的关键调节机制提供深入的见解和/或支持。其次，流出组织的硒处理可能会提供一种新型的青光眼模型，以控制分子和细胞水平的流出途径的变化。 如果成功，则从这些研究中获得的结果将提供对硒对水溶液的影响的基本理解，发现新颖的治疗靶标可用于青光眼治疗，并为未来的研究奠定了基础。