OXIDATIVE STRESS AND UVEAL NOREPINEPHRINE RELEASE

过氧化氢 (H2O2) 是一种生物衍生的稳定形式的“活性物质” 氧气存在于眼前节的几个组织中 眼睛。 尽管前房内或玻璃体内注射 H2O2 已被证明可引起组织的显着形态变化 前葡萄膜，尚无研究探讨其潜在的药理学作用 H2O2 对眼前节的影响。 这些研究是 需要，因为 H2O2 可能会干扰自主神经传递 前葡萄膜中的神经，进而影响房水 动态。 此外，H2O2 可能会改变受体的药理学， 它们在前葡萄膜中的信号转导途径以某种方式 与大脑和一些外周组织中报道的相似。 我们假设 H2O2 诱导的氧化应激可以改变 虹膜睫状体交感神经去甲肾上腺素（NE）的输出 身体。 H2O2 引起的效应可能会通过效应影响 NE 的输出 释放过程和/或通过对活性的影响 交感神经末梢上的交界前受体。 的 因此，本研究的总体目标是调查 H2O2 对家兔虹膜睫状体 NE 释放的影响。 本项目中的实验旨在回答 以下问题：(i) H2O2 是否会改变释放和/或 前葡萄膜中 NE 的可用性：(ii) 是第二信使，例如 由于钙、cGMP、cAMP 和前列腺素参与所引起的影响 H2O2 对交感神经传递的影响：(iii) 有关系吗 过氧化氢酶活性、H2O2 水平与 NE 和 NPY 输出之间的关系 房水和虹膜-睫状体：(iv) 低眼压吗 H2O2 的影响涉及交感神经传递的变化和/或 前列腺素释放？ 综上所述，我们将检查 H2O2 的影响 对兔子虹膜-纤毛的基础和诱发去甲肾上腺素释放的影响 身体在体外和体内。 这项研究的结果将会改善 我们对 H2O2 对神经传递影响的理解并将 增进我们对氧化应激诱导损伤机制的了解 在前葡萄膜中。 此外，我们希望这些研究能够揭示 H2O2 在眼部生理学和/或药理学中的新作用。 我们 预计该项目的研究结果将适用于 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.