OXIDATIVE STRESS AND UVEAL NOREPINEPHRINE RELEASE

过氧化氢(H_2O_2)是一种生物衍生的稳定形式的活性 氧存在于关节前节段的几个组织中 眼睛。尽管房内或玻璃体内注射过氧化氢有 显示出能引起大鼠脑组织发生显著的形态变化 前葡萄膜，还没有研究涉及潜在的药理作用 双氧水对眼前段的影响。这些研究是 因为过氧化氢可能会干扰自主神经中的神经传递 前葡萄膜中的神经反过来可能影响房水 动力学。此外，过氧化氢可能会改变受体的药理作用，并 它们在前葡萄膜中的信号转导通路在某种程度上 与在大脑和一些外周组织中报道的类似。 我们假设，过氧化氢诱导的氧化应激可以改变 虹膜睫状体交感神经的去甲肾上腺素(NE)输出 尸体。过氧化氢引起的效应可能通过某种效应影响去甲肾上腺素的输出 关于释放过程和/或通过对活性的影响 交感神经末梢上有交感前受体。这个 因此，本研究的总体目标是调查 过氧化氢对兔虹膜睫状体去甲肾上腺素释放的影响 本项目中的实验旨在回答以下问题 以下问题：(I)过氧化氢是否改变了释放和/或 去甲肾上腺素在前葡萄膜的可用性：(Ii)是第二信使 如钙、cGMP、cAMP和前列腺素等参与了引起的效应 H_2O_2对交感神经传递的影响：(III)两者之间有关系吗 过氧化氢酶活性、H_2O_2水平与去甲肾上腺素和神经肽Y产量的关系 房水和虹膜睫状体：(四)降眼压 H_2O_2的作用涉及交感神经传递和/或 前列腺素释放？综上所述，我们将研究过氧化氢的影响 兔虹膜睫状肌基础和诱发去甲肾上腺素释放的研究 体外和体内的体内实验。这项研究的结果将会有所改善 我们对过氧化氢对神经传递和意志的影响的理解 提高对氧化应激损伤机制的认识 在前葡萄膜上。此外，我们希望这些研究可以揭示 过氧化氢在眼生理和/或药理学中的新作用。我们 预计本项目的调查结果将适用于 眼前节疾病，如青光眼、葡萄膜炎或 白内障。

Hydrogen peroxide (H2O2) is a biologically derived stable form of 'active oxygen' which is present in several tissues of the anterior segment of the eye. Although intracameral or intravitreal injections of H2O2 have shown to induce significant morphological changes in tissue of the anterior uvea, no study has addressed the potential pharmacological effect of H2O2 in the anterior segment of the eye. These studies are needed because H2O2 may interfere with neurotransmission in autonomic nerves in the anterior uvea which in turn could affect aqueous humor dynamics. Furthermore, H2O2 may alter the pharmacology of receptors and their signal transduction pathways in the anterior uvea in a manner similar to that reported in the brain and in some peripheral tissues. We hypothesize that oxidative stress induced by H2O2 can modify the output of norepinephrine (NE) from sympathetic nerves in the iris-ciliary body. Effects caused by H2O2 may affect the output of NE by an effect on the release process and/or via an effect on the activity of prejunctional receptors located on sympathetic nerve terminals. The overall objective of the present study is, therefore, to investigate the effect of H2O2 on NE release from the rabbit iris-ciliary body. Experiments in the present project have been designed to answer the following questions: (i) does H2O2 alter the release and/or availability of NE in the anterior uvea: (ii) are second messengers such as calcium, cGMP, cAMP and prostaglandins involved in the effects caused by H2O2 on sympathetic neurotransmission: (iii) is there a relationship between catalase activity, H2O2 levels and the output of NE and NPY in the aqueous humor and iris-cillary body: (iv) does ocular hypotensive effects of H2O2 involve changes in sympathetic neurotransmission and/or prostaglandin release? In summary, we will examine the effect of H2O2 on basal and evoked norepinephrine release in the rabbit iris-ciliary body both in vitro and in vivo. The results of this study will improve our understanding of the effect of H2O2 on neurotransmission and will advance our knowledge of the mechanism of oxidative stress induced damage in the anterior uvea. Furthermore, we hope that these studies may reveal a new role for H2O2 in ocular physiology and/or pharmacology. We anticipate that the findings of this project will be applicable to diseases of the anterior segment of the eye such as glaucoma, uveitis or cataracts.