TRACE ELEMENT DYNAMICS IN THE VERTEBRATE EYE

该实验室在目前的几项重大发现 资金期间表明，铁（Fe）的可用性的监管是一个 眼内环境稳定的重要组成部分，铁的可用性可能 在眼部病理学中起着关键作用。 在目前的提案中，我们 我计划更详细地调查这些观察结果， 在正常人和正常人的透镜中， 病理条件。 要解决的假设是， 晶状体对铁的吸收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 白内障形成，导致晶状体铁浓度增加。 晶状体功能的有害变化，然后发生由于铁催化 氧化反应。 由于铁的重要性， 眼病理生理学，因为目前几乎一无所知 关于眼铁稳态，本建议中的实验旨在 填补这个空白。 这些研究将从使用透镜上皮细胞的实验开始开始 然后将其扩展到整个透镜培养物，最后 体内情况。 铁在土壤中的运输和储存机制 透镜将使用整个兔晶状体和上皮细胞来定义 正常兔和犬晶状体的培养物，以及犬白内障的培养物 眼镜. 透镜体运输和储存的容量限制 Fe将被确定。 超容对透镜的影响 功能和这些变化背后的机制将是 测定 由于透镜可能是一个重要的调节器， 在体眼铁稳态，无晶状体眼对眼铁的影响 将确定正常和发炎眼睛中的内稳态。 结果 这些实验将提供必要的信息， 铁稳态及透镜对眼铁的贡献 体内平衡 详细介绍了铁在眼内的作用， 病理学可能为合理设计 新的和更有效的治疗方案。

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.