PERFUSED TRABECULAR MESHWORK AS A MODEL FOR OUTFLOW

灌注小梁网作为流出模型

• 批准号: 3264190
• 负责人: KRISTINE A ERICKSON
• 金额: $ 13.81万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3264190
• 关键词: adrenergic receptor; alternatives to animals in research; atrial natriuretic peptide; biological models; cell cell interaction; chymotrypsin; cyclic AMP; cyclic GMP; cytochalasins; drug metabolism; epinephrine; ethylenediaminetetraacetate; eye pharmacology; histochemistry /cytochemistry; human tissue; intraocular aqueous flow; intraocular fluid; nitroglycerin; perfusion; physiology; tissue /cell culture; trabecular meshwork

The overall goal of proposed research is to gain further knowledge of the of the physiology and pharmacology of aqueous outflow in the human eye. Enhanced understanding of the basic mechanism(s) underlying normal outflow physiology may lead to greater insight into the pathogenesis of primary open angle glaucoma (POAG). Although, the monkey eye in vivo has been a valuable model in understanding basic concepts of outflow physiology, the recent concern over the use of primates in biomedical research dictates the need for acceptable alternatives to animal experimentation. Furthermore, the monkey eye is not an optimal model, since monkeys rarely if ever develop POAG. The experimental system to be used in these studies is the perfused human outflow tissue model. This newly developed model involves placement of the eviscerated (e.g. lens and uveal tissue are removed) anterior corneoscleral shell with attached trabecular meshwork (TM) onto a specialized perfusion apparatus. The TM and associated outflow tissues are perfused with culture medium at a physiologically-relevant perfusion pressure in a 5% C02 environment at 37 degree C. Under these conditions, the perfused TM is similar to the human outflow system in vivo for several days with regard to morphology as well as functional parameters. Of considerable interest is the finding that epinephrine increases outflow facility in the perfused TM model. This finding illustrates the potential importance of this model in the study of aqueous outflow dynamics, since this is the only in vitro system in which an epinephrine-induced outflow facility increase has been demonstrated. The specific aims of this proposal are: 1) to further characterize the perfused TM model; 2) to define the mechanism of action of the epinephrine-induced facility increase as well as investigate the effects of other "trabecular acting" drugs; and 3) to define morphological correlates of physiological findings. The ability to study the epinephrine responsive human outflow tissues for a period of several days along with the opportunity to establish a model which serves as an alternative to animal testing clearly points to the potential importance of his model in investigating the biology of the outflow pathway system.

拟议研究的总体目标是获得进一步的知识 房水流出的生理学和药理学研究 人眼。提高对基本机制的认识(S) 潜在的正常流出生理可能会带来更大的洞察力 探讨原发性开角型青光眼(POAG)的发病机制。 尽管，体内的猴眼一直是一个有价值的模型 理解流出生理学的基本概念，最近 对在生物医学研究中使用灵长类动物的担忧 需要可接受的替代动物实验的方法。 此外，猴眼并不是最理想的模型，因为猴子 极少发生POAG。将要使用的实验系统 在这些研究中是灌流的人体流出组织模型。这 新开发的模型包括放置被剔除的内脏(例如 摘除晶状体和葡萄膜组织)前角巩膜 与Trabecular Network(TM)连接到专门的 灌注器。TM和相关流出组织为 在生理上相关的培养基上灌流 在37℃、5%的二氧化碳环境中的灌流压力 在这些情况下，灌流的TM类似于人类的流出 体内系统在形态方面也有几天的时间 作为函数参数。令人相当感兴趣的是这个发现 肾上腺素增加灌流的TM的流出功能 模特。这一发现说明了这一点的潜在重要性。 模型来研究水的外流动力学，因为这是 只有在体外系统中肾上腺素诱导外流 设施的增加已经得到了证明。这样做的具体目的是 建议包括： 1)对灌流TM模型进行进一步的表征； 2)明确肾上腺素的作用机制 设施增加以及调查其他 “骨小梁作用”药物；以及 3)明确生理学发现的形态相关性。 研究肾上腺素反应性人体流出的能力 为期几天的纸巾，同时有机会 建立可替代动物试验的模型 清楚地指出了他的模型在 研究流出通道系统的生物学。