TRACE METAL DYNAMICS IN THE VERTEBRATE EYE

追踪脊椎动物眼睛中的金属动力学

• 批准号: 3447744
• 负责人: MARY C McGahan
• 金额: $ 5.17万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-01-01 至 1986-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3447744
• 关键词: active transport; atomic absorption spectrometry; blood aqueous barrier; copper; dietary trace element; ferroxidase; fresh water environment; hyaluronate; immunochemistry; inflammation; intraocular fluid; membrane permeability; penicillamine; radiotracer; trace elements

Preliminary findings from an ongoing project indicate that after an episode of uveitis in the copper (Cu) concentration in the intraocular fluids (IOFs) remains higher than in control eyes even after the protein concentration has returned toward normal. At this time the Cu/protein ratio is higher in the IOFs than in control eyes or in blood plasma. The goal of this research proposed is to elucidate the mechansim which determines normal Cu concentrations within intraocular compartments and to determine whether after inflammation the elevated Cu concentration in the IOFs is due to an increased Cu permeability of the blood ocular barriers, or is due to some other mechanism. Alternate mechanisms to be investigated are a prolonged inhibition of an absorptive Cu transport or the loading of some tissue with Cu during the acute phase of inflammation followed by slow Cu release into the IOFs. The amount of Cu present in the free state or bound to proteins, such as ceruloplasmin, in IOFs and present in tissues normally and during various stages of inflammation will be determined. High Cu concentrations can be toxic to cellular membranes and Cu has also been shown to catalyze the breakdown of hyaluronic acid. Thus, prolonged elevation of Cu concentration in the IOFs may contribute to some of the deleterious long-term effects of inflammation on intraocular tissues such as the damage suffered by the transport functions of the ciliary processes. The possible role of Cu in inflammation-induced tissue damage and loss of transport function will be investigated by inducing experimental uveitis in animals whose plasma Cu concentration is greatly reduced by pretreatment with penicillamine and/or Cu free diet and comparing the observed intra-ocular tissue damage to that observed in normal animals or animals which were preloaded with Cu before the induction of experimental uveitis. Finally, the possibility that inflammation causes a prolonged alteration in the intra-ocular fluid concentration of other trace metals such as selenium, manganese, lead, iron, etc., will be investigated. Any trace metal in preliminary experiments that shows a behavior similar to that of Cu will then be studied in detail in a manner similar to that described for Cu. Experimental animals to be used will be rabbits, toads, cats, and primates.

正在进行的项目的初步调查结果表明，在一次事件发生后 眼内液中铜 (Cu) 浓度对葡萄膜炎的影响 即使在蛋白质注射后，（IOF）仍然高于对照眼 浓度已恢复正常。 此时Cu/蛋白质 IOF 中的比率高于对照眼或血浆中的比率。 这 这项研究的目的是阐明这一机制 确定眼内室内的正常铜浓度并 确定炎症后铜浓度是否升高 IOFs 是由于血眼屏障的铜渗透性增加所致， 或者是由于某些其他机制造成的。 有待研究的替代机制 是对铜吸收转运或负载的长期抑制 在炎症的急性期，一些组织含有铜，随后是缓慢的炎症期 Cu 释放到 IOF 中。 以游离态存在的 Cu 量或 与 IOF 中的蛋白质（例如铜蓝蛋白）结合并存在于组织中 正常情况下以及在炎症的各个阶段将被确定。 高浓度的铜可能对细胞膜有毒，并且铜还会 已被证明可以催化透明质酸的分解。 于是，延长了 IOF 中铜浓度的升高可能会导致某些 炎症对眼内组织的有害长期影响，例如 由于睫状体的运输功能受到损害 流程。 Cu 在炎症引起的组织损伤中的可能作用 运输功能的丧失将通过诱导进行调查 血浆铜浓度显着升高的动物实验性葡萄膜炎 通过用青霉胺和/或不含铜的饮食进行预处理来减少和 将观察到的眼内组织损伤与观察到的进行比较 正常动物或诱导前预载铜的动物 实验性葡萄膜炎。 最后，有可能是炎症引起的。 其他眼内液体浓度的长期变化 微量金属，如硒、锰、铅、铁等 调查了。 初步实验中显示出的任何痕量金属 然后将以某种方式详细研究与 Cu 类似的行为 与针对 Cu 的描述类似。 所使用的实验动物将 兔子、蟾蜍、猫和灵长类动物。