EICOSANOIDS--OCULAR PHYSIOLOGY AND PHARMACOLOGY

一些二十烷类化合物(EDs)，如前列腺素及其衍生物， 在所有被研究的动物身上都被证明是有效的降眼压药物 在血压正常的人类志愿者中也是如此。然而，急救人员和其他人一样 药物有副作用，除非它们能被减少或消除， 可能会限制这些物质在长期临床上的有效性 慢性青光眼的治疗。这个项目的目标是获得一个 按顺序清楚地了解EDS的眼部效应机制 提供发展电子数据系统所需的基本资料，包括 长期维持极量降眼压的有效药物 眼部和全身副作用。我们将进行一次彻底的 对以下特定区域进行调查：1)眼睛 EDS的药代动力学研究将特别参考 正畸缓释系统，使用体内示踪技术和 体外通透性研究2)ED降眼压机制的研究 将包括分泌物、假性设施、常规和葡萄膜巩膜 外流，使用荧光光度法、同位素稀释法、色调照相法和 灌流技术。3)其他眼睛效应的机制将是 研究包括散瞳(瞳孔造影术，ED对孤立虹膜的影响 肌肉)和结膜充血(示踪剂研究)以及分解 血-房水屏障(廷德尔效应和蛋白质的测量 集中)在闪光的物种(猫、灵长类和兔子)中 发展到了非常不同的程度。对互联网的基本认识 EDS Will的药代动力学、作用机制和副作用 提供有效使用眼睛所必需的信息 眼科医生用于临床治疗的低血压急救药物 青光眼。这样的理解对于审议也是至关重要的。 EDS在眼科治疗的其他领域中的应用以及 第二代和第三代青光眼药物。这种可能性仍然存在 然而，存在能有效降低正常血压的眼压的ED 人类受试者对青光眼不会有同样的影响。如果这个 事实证明，我们的研究将对以下方面做出重要贡献 对青光眼的理解，因为这种缺乏效果将意味着 青光眼与青光眼的ED系统某些方面的缺陷有关 前段。简而言之，这种多管齐下的方法将使 对眼科研究和青光眼研究的重要贡献 特别是无论急诊室是否像我们相信的那样，提供 青光眼内科治疗的新途径。

Some eicosanoids (EDs), such as prostaglandins and their derivatives, have been shown to be effective ocular hypotensive agents in all animals studied as well as in normotensive human volunteers. However, EDs, like other drugs, have side effects which, unless they can be reduced or eliminated, may limit the usefulness of these substances in the long-term clinical management of chronic glaucomas. The goal of this project is to gain a clear understanding of the mechanisms of the ocular effects of EDs in order to provide the basic information required for the development of EDs as effective drugs for the long-term maintenance of IOP reduction with minimal ocular and systemic side effects. We shall undertake a thorough investigation of the following specific areas: 1) The ocular pharmacokinetics of EDs will be studied with special reference to an orthorectified slow-release system, using in vivo tracer techniques and in vitro flux studies; 2) studies on the mechanism of ED-induced IOP reduction will include secretion, pseudofacility, and conventional and uveoscleral outflow, using fluorophotometry, isotope dilution, tonography, and perfusion techniques. 3) The mechanism of other ocular effects will be studied, including miosis (pupillography, ED effects on isolated iridial muscles) and conjunctival hyperemia (tracer studies), as well as breakdown of the blood aqueous barrier (measurement of Tyndall effect and protein concentration) in species (cats, primates, and rabbits) in which flare develops to greatly different extents. A basic understanding of the pharmacokinetics, mechanisms of action, and side effects of EDs will provide the information essential for the effective use of ocular hypotensive EDs by ophthalmologists for the clinical management of glaucomas. Such understanding will also be essential for the consideration of EDs in other areas of ocular therapeutics and for the development of second and third generations of glaucoma drugs. The possibility still exists, however, that EDs, which effectively reduce IOP in normotensive human subjects, do not have the same effect on glaucomatous eyes. If this proves to be the case, our studies will make an important contribution to the understanding of glaucoma, since such lack of effect would imply that glaucoma is associated with a defect in some aspects of the ED system of the anterior segment. In short, this multipronged approach will make an important contribution to eye research in general and to glaucoma research in particular whether or not EDs do, as we believe that they will, provide a new approach to the medical management of glaucoma.