TRACE ELEMENT DYNAMICS IN THE VERTEBRATE EYE

脊椎动物眼中的微量元素动态

• 批准号: 3259505
• 负责人: MARY C McGahan
• 金额: $ 14.51万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3259505
• 关键词: antioxidants; binding proteins; catalyst; chelation therapy; chemical structure function; deferoxamine; electroretinography; endotoxins; eye infections; eye pharmacology; free radicals; inflammation; intraocular fluid; iron; laboratory rabbit; metal poisoning; nonhuman therapy evaluation; oxidation reduction reaction; trace elements; uveitis

The ocular toxicity of iron (Fe) has been clearly documented in relation to the effects of Fe containing intraocular foreign bodies and hemorrhage. There is now a growing body of evidence which implicates Fe as an integral part of the ocular inflammatory response and associated tissue damage. Much of the work done in the past has centered on histologic and electroretinogram changes induced by Fe. The experiments described in this proposal are designed to integrate biochemical, structural and functional studies of Fe toxicity and to provide new insights into Fe's role in the ocular inflammatory response. The toxic effects of Fe are likely due to its ability to catalyze free radical reactions. Under normal physiologic circumstances, Fe is bound to proteins and cannot catalyze free radical formation. However, Fe can be released from its binding proteins in pathological conditions and can then catalyze these reactions. In an ongoing project in this laboratory methods have been developed for measurement of Fe, total-iron-binding capacity, and "free" catalytic Fe in the intraocular fluids (IOFs) and plasma. In an experimental model, the Fe concentration of the inflamed IOFs was increased more than 20 times that of the uninflamed control eyes. Furthermore, "free" catalytic Fe was found in the inflamed IOFs. In this proposal, the relationship between the presence of "free" Fe and the conditions which increase the likelihood of Fe's release from its binding proteins on parameters of ocular inflammation and tissue damage will be determined using the endotoxin model of ocular inflammation in rabbits. Tissue damage parameters will include changes in electroretinogram, vitreal liquefaction and retinal lipid peroxidation. In a related set of experiments, Fe will be injected intravitreally to determine the threshold level for its damaging effects. The effects of the Fe-chelator desferrioxamine and the endogenous antioxidant Fe-binding protein transferrin will also be explored. In all of the planned experiments the relationship between the amount of "free" Fe in the IOFs, the extent of the inflammatory response and changes in IOF biochemistry and ocular structure and function will be determined. It is likely that further elucidation of Fe's role in the biochemical changes which occur during ocular inflammation will lead to therapeutic advances in the treatment of this ocular pathology.

铁 (Fe) 的眼毒性已被清楚地记录在案 含铁眼内异物的影响 出血。 现在有越来越多的证据表明铁 作为眼部炎症反应的一个组成部分和相关的 组织损伤。 过去所做的大部分工作都集中在 Fe 引起的组织学和视网膜电图变化。 实验 该提案中描述的目的是整合生化、 铁毒性的结构和功能研究并提供新的 深入了解铁在眼部炎症反应中的作用。 Fe 的毒性作用可能是由于它能够催化游离 自由基反应。 正常生理情况下，Fe结合 与蛋白质结合，不能催化自由基的形成。 然而，铁可以 在病理条件下从其结合蛋白中释放出来，并且可以 然后催化这些反应。 在该实验室正在进行的项目中 已开发出测量铁、总铁结合的方法 能力，以及眼内液（IOF）中的“游离”催化铁和 等离子体。 在实验模型中，发炎的 Fe 浓度 IOF 比未发炎对照增加了 20 倍以上 眼睛。 此外，在发炎的 IOF 中发现了“游离”催化 Fe。 在该提案中，“游离”Fe 的存在与 增加 Fe 从其中释放的可能性的条件 结合蛋白对眼部炎症和组织损伤参数的影响 将使用眼部炎症的内毒素模型来确定 兔子。 组织损伤参数将包括变化 视网膜电图、玻璃体液化和视网膜脂质过氧化。 在一组相关的实验中，Fe 将被注射到玻璃体内 确定其破坏性影响的阈值水平。 的影响 Fe-螯合剂去铁胺和内源性抗氧化剂 Fe-结合 还将探索蛋白质转铁蛋白。 在所有计划的 实验了 IOF 中“游离”Fe 含量之间的关系， 炎症反应的程度和 IOF 生化的变化 并确定眼睛的结构和功能。 很可能是这样 进一步阐明铁在发生的生化变化中的作用 眼部炎症期间的治疗将导致治疗进展 治疗这种眼部病变。