TRACE ELEMENT DYNAMICS IN THE VERTEBRATE EYE

该实验室在当前的几个重要发现 资金期表明，对铁(Fe)有效性的监管是一种 眼内稳态关键成分，铁的可利用性可能 在眼部病理中起着举足轻重的作用。在目前的提案中，我们 计划更详细地调查这些观察结果并澄清 正常人和正常人晶状体中铁储存的机制 病理情况。需要解决的假设是 晶状体对铁的摄取和储存对眼内环境的稳定至关重要 在正常情况下。这种能力在炎症或 白内障的发生，导致晶状体铁浓度升高。 由于铁的催化，晶状体功能会发生有害的变化 氧化反应。因为铁的重要性已被证明 眼睛的病理生理学，因为目前几乎什么都不知道 关于眼部铁稳态，本提案中的实验旨在 填补这一空白。 这些研究将从使用晶状体上皮细胞的实验开始 文化，然后将扩展到整个镜头文化，最后 活体情况。铁在土壤中的运输和储存机制 将使用完整的兔晶状体和上皮细胞来定义晶状体 正常兔、犬晶状体和犬性白内障的培养 隐形眼镜。透镜的运输和储存能力的限度 铁将被确定。超容对晶状体的影响 函数和这些更改背后的机制将是 下定决心。因为透镜很可能是一个重要的调节器 眼铁体内动态平衡及无晶状体眼对眼铁的影响 正常和发炎眼睛的动态平衡将被确定。结果是 这些实验将提供有关透镜的基本信息 铁的动态平衡与晶状体对眼内铁的贡献 动态平衡。详细介绍铁在眼部的作用 病理学很可能为合理设计 新的更有效的治疗方案。

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.