OXIDATIVE STRESS AND UVEAL NOREPINEPHRINE RELEASE

过氧化氢（H2 O2）是一种生物衍生的稳定形式的“活性” 氧“，这是目前在几个组织的前段， the eye. 虽然前房内或玻璃体内注射H2 O2， 显示诱导组织的显著形态学变化， 前葡萄膜，没有研究已经解决了潜在的药理学 H2 O2对眼前节的影响。 这些研究 因为H2 O2可能会干扰自主神经系统的神经传递， 前葡萄膜中的神经，其又可影响房水 动力学 此外，H2 O2可改变受体的药理学， 它们在前葡萄膜中的信号传导途径 类似于在脑和一些外周组织中报道的。 我们推测，H2 O2诱导的氧化应激可以改变细胞内的 虹膜睫状体中交感神经的去甲肾上腺素（NE）输出 身体 H2 O2引起的效应可能通过一种效应影响NE的输出 对释放过程和/或通过对活性的影响， 位于交感神经末梢上的连接前受体。 的 因此，本研究的总体目标是调查 H_2O_2对兔虹膜睫状体释放NE的影响。 本项目中的实验旨在回答 （i）H2 O2是否改变释放和/或 在前葡萄膜NE的可用性：（ii）是第二信使， 如钙、cGMP、cAMP和三尖杉酯碱参与引起的效应 H2 O2对交感神经传递的影响：（iii）是否存在关系 过氧化氢酶活性、H_2O_2水平与NE和NPY的分泌之间存在着一定的相关性。 眼房水和虹膜-睫状体：（iv）眼水肿 H2 O2的影响涉及交感神经传递的变化和/或 前列腺素释放 总之，我们将研究H2 O2的作用 对家兔虹膜睫状体基础和诱发去甲肾上腺素释放的影响 无论是在体外还是在体内。 这项研究的结果将改善 我们对H2 O2对神经传递的影响的理解， 促进我们对氧化应激损伤机制的认识 在前葡萄膜 此外，我们希望这些研究可以揭示 H2 O2在眼生理学和/或药理学中的新作用。 我们 预计该项目的结果将适用于 眼睛前段的疾病，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.