Effect of Isoprostanes on Retinal Transmitter Release

超出所提供的空间。异prostanes （IsoP’s）是一系列类似前列腺素的化合物，在体内由非酶、自由基催化花生四烯酸的过氧化作用大量形成，不依赖于环加氧酶。除了提供体内和体外氧化应激的可靠测量外，IsoP还可以在某些组织中发挥药理作用。文献综述表明，很少有研究涉及IsoP对中枢或外周组织神经递质释放的影响。虽然有报道称IsoP可调节葡萄膜前组织的交感神经传递，但尚未有研究调查这些化合物对视网膜神经传递的潜在调节作用。在本研究中，我们将在体外和体内验证IsoP可以调节谷氨酸、γ -氨基丁酸（GABA）和多巴胺能在视网膜中的传递的假设。本研究的总体目的是研究不同系列的IsoP （A1, El, E2, F1， F2和F3）在体外和体内对视网膜谷氨酸，GABA和多巴胺释放的影响。因此，本项目的实验旨在回答以下问题：(i)在体外和体内，不同的IsoP是否会改变谷氨酸、GABA和多巴胺的释放和/或可用性？（ii） IsoP产生的效果是否可与其他花生四烯酸代谢物（前列腺素和凝血素）相媲美？（iii）突触前异源受体在这些化合物对谷氨酸、GABA和多巴胺的体外和体内影响中的作用是什么？我们期望本研究的结果将提高我们对IsoP影响视网膜谷氨酰胺能、gaba能和多巴胺能传递的基本机制的理解。此外，这些研究可能揭示视网膜中IsoP作用的药理学/毒理学可及部位。我们希望本项目的观察结果能够适用于与自由基产生和氧化损伤相关的视网膜疾病，如缺血、青光眼、糖尿病视网膜病变、老年性黄斑变性等。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. Isoprostanes (IsoP's) are a series of prostaglandin-like compounds that are formed in abundance in vivo by a non-enzymatic, free radical catalyzed peroxidation of arachidonic acid independent of cyclooxygenase. In addition to providing a reliable measure of in vivo and in vitro oxidative stress, IsoP's can exert pharmacological effects in some tissues. A review of litrature revealed that very few studies have addressed the effects of IsoP's on neurotransmitter release from central or peripheral tissues. Although IsoP's have been reported to modulate sympathetic neurotransmission from anterior uveal tissues, no studies have investigated the potential regulatory effects of these compounds on neurotransmission in the retina. In the present study, we will test the hypothesis that IsoP's can modulate glutamate, gamma-aminobutyric acid (GABA) and dopaminergic transmission in the retina both in vitro and in vivo. The overall objective of the present study is to examine the effect of different series of IsoP's (A1, El, E2, F1, F2 and F3) on glutamate, GABA and dopamine release from retinae both in vitro and in vivo. Experiments in this project have, therefore, been designed to answer the following questions: (i) do different IsoP's alter the release and/or availability of glutamate, GABA and dopamine in vitro and in vivo? (ii) are the effects produced by IsoP's comparable to those of other arachidonic acid metabolites (prostaglandins and thromboxanes)? (iii) what is the role of presynaptic IsoP heteroreceptors in the effects caused by these compounds on glutamate, GABA and dopamine in vitro and in vivo? We anticipate that the results of the present study will improve our understanding of the basic mechanisms involved in the effects of IsoP's on retinal glutaminergic, GABAergic and dopaminergic transmission. Furthermore, these studies may reveal pharmacologically/toxicologically accessible sites for the action of IsoP's in the retina. We hope that observations made in this project will be applicable to diseases of the retina associated with the generation of free radicals and oxidative damage such as such as ischemia, glaucoma, diabetic retinopathy and age-related macular degeneration. PERFORMANCE SITE ========================================Section End===========================================