TRACE ELEMENT DYNAMICS IN THE VERTEBRATE EYE

脊椎动物眼中的微量元素动态

• 批准号: 3259502
• 负责人: MARY C McGahan
• 金额: $ 18.95万
• 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 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3259502
• 关键词: adenosine triphosphate; animal tissue; biological transport; cataract; chelating agents; diene; enzyme activity; epithelium; eye; eye disorder; ferritin; glyceraldehyde 3 phosphate dehydrogenase; homeostasis; interleukin 1; iron; laboratory rabbit; lens; organ culture; oxidation reduction reaction; pathologic process; radiotracer; rubidium; statistics /biometry; tissue /cell culture; trace elements; transferrin; tumor necrosis factor alpha

Several significant findings from this laboratory during the current funding period indicate that regulation of iron (Fe) availability is a crucial component of ocular homeostasis, and that availability of Fe may play a pivotal role in ocular pathology. In the current proposal, we plan to investigate these observations in greater detail and to elucidate the mechanisms involved in Fe storage in the lens in normal and pathological conditions. The hypothesis to be addressed is that lenticular uptake and storage of Fe is essential for ocular homeostasis under normal conditions. This ability is compromised in inflammation or cataractogenesis, resulting in increased lenticular Fe concentration. Deleterious changes in lenticular function then occur due to Fe-catalyzed oxidative reactions. Because of the demonstrated importance of Fe to ocular pathophysiology and because virtually nothing is presently known about ocular Fe homeostasis, experiments in this proposal are designed to fill this gap. These studies will begin with experiments using lens epithelial cell cultures and then will be extended to whole lens cultures and finally to the in vivo situation. Mechanisms for Fe transport and storage in the lens will be defined using both whole rabbit lenses and epithelial cell cultures from normal rabbit and canine lenses, and canine cataractous lenses. The limits of lenticular capacity for transport and storage of Fe will be determined. The effects of exceeding capacity on lens function and the mechanisms underlying these alterations will then be determined. Since the lens is likely to be an important regulator of ocular Fe homeostasis in vivo, the effects of aphakia on ocular Fe homeostasis in normal and inflamed eyes will be determined. The results of these experiments will provide essential information about lenticular Fe homeostasis and about the contributions of the lens to ocular Fe homeostasis. Detailed information about the functions of Fe in ocular pathology is likely to provide important insights for rational design of new and more effective therapeutic regimes.

该实验室在当前的几个重要发现 资助期限表明铁（Fe）供应的监管是一个 眼稳态的重要组成部分，铁的可用性可能 在眼部病理学中发挥着关键作用。 在当前的提案中，我们 计划更详细地调查这些观察结果并阐明 正常和正常情况下晶状体中 Fe 储存的机制 病理状况。 要解决的假设是 晶状体对铁的吸收和储存对于眼内稳态至关重要 正常情况下。 这种能力在炎症或 白内障发生，导致晶状体铁浓度增加。 由于 Fe 催化，晶状体功能发生有害变化 氧化反应。 由于铁的重要性已被证明 眼部病理生理学，因为目前几乎一无所知 关于眼部铁稳态，本提案中的实验旨在 填补这个空白。 这些研究将从使用晶状体上皮细胞的实验开始 文化，然后扩展到整个镜片文化，最后扩展到 体内情况。 铁的运输和储存机制 晶状体将使用整个兔晶状体和上皮细胞来定义 正常兔子和犬晶状体以及犬白内障的培养物 镜头。 光栅运输和储存能力的限制 Fe将被测定。 超容量对镜片的影响 这些改变背后的功能和机制将被 决定。 由于镜头可能是一个重要的调节器 体内眼部 Fe 稳态，无晶体眼对眼部 Fe 的影响 将确定正常和发炎眼睛的体内平衡。 结果 这些实验将提供有关双凸透镜的重要信息 Fe 稳态以及晶状体对眼 Fe 的贡献 体内平衡。 关于铁对眼的功能的详细信息 病理学可能为合理设计提供重要见解 新的、更有效的治疗方案。