TRACE ELEMENT DYNAMICS IN THE VERTEBRATE EYE

白内障的形成是一个重大的健康和经济问题。虽然 白内障发生的确切机制尚不清楚， 有力地证明了氧化损伤是 这个过程。铁催化氧化反应， 对透镜蛋白质、DNA和膜的损伤， 与白内障晶状体的损伤类型相似。铁 储存蛋白铁蛋白可以保护细胞免受氧化损伤 通过安全地隔离大量的铁的重要性 铁蛋白对正常透镜功能的作用， 研究发现，患有显性遗传异常的人， 铁蛋白合成表现出早期双侧白内障。PI发现 透镜上皮细胞合成铁蛋白，抗坏血酸 酸和谷胱甘肽增加铁蛋白浓度， 有害的氧化剂，过氧化氢减少铁蛋白的合成。 因此，她推测：在透镜中， 铁蛋白是透镜抗氧化剂的重要组成部分 潜力 抗坏血酸增加从头铁蛋白合成， 铁结合到这种蛋白质中，从而保护透镜 免受氧化损伤 过氧化氢，除了直接 损害透镜细胞，降低透镜的抗氧化能力， 降低铁蛋白合成。基于这一假设， 具体目标是确定时间和浓度依赖性 抗坏血酸、谷胱甘肽、铁和过氧化氢的影响 对铁蛋白合成、亚基组成、亚细胞 定位，以及结合铁的能力。此外该 铁蛋白保护透镜上皮细胞免受 氧化损伤将通过增加铁蛋白来确定 在这些细胞暴露于损伤之前， 过氧化物的浓度。这些实验的结果将 提供关于铁蛋白和抗坏血酸的作用的关键信息 酸在透镜中的铁代谢中起作用，并可提供特定的 支持抗坏血酸使用的保护性生化机制 补充酸以预防白内障进展。

Cataract formation is a major health and economic problems. Although the exact mechanisms underlying cataractognesis are not known, there is compelling evidence that oxidative damage is a major component of this process. Iron catalyzes oxidative reactions and causes damage to lens proteins, DNA and membranes which is similar to the type to the type of damage found in cataractous lenses. The iron storage protein, ferritin, can protect cells from oxidative damage by safely sequestering large amounts of iron. The importance of ferritin to normal lens function is underscored by the recent finding that humans with a dominantly inherited abnormality in ferritin synthesis exhibit early bilateral cataracts. The PI found that the lens epithelial cells synthesize ferritin, that ascorbic acid and glutathione increase ferritin concentration and that the damaging oxidant, hydrogen peroxide decreases ferritin synthesis. Therefore, she hypothesizes that: In the lens, the iron-binding capability of ferritin is a critical component of lens antioxidant potential. Ascorbic acid increases de novo ferritin synthesis and iron incorporation into this protein, thereby protecting the lens from oxidative damage. Hydrogen peroxide, in addition to directly damaging lens cells, decreases lens antioxidant potential by decreasing ferritin synthesis. Based upon this hypothesis the specific aims are to determine the time and concentration dependent effects of ascorbic acid, glutathione, iron and hydrogen peroxide on ferritin synthesis, subunit composition, subcellular localization, and ability to incorporate iron. In addition, the ability of ferritin to protect lens epithelial cells against oxidative damage will be determined by increasing ferritin concentration in these cells prior to exposing them to damaging concentrations of peroxide. The results of these experiments will provide key information regarding the roles of ferritin and ascorbic acid in iron metabolism in the lens and may provide a specific protective biochemical mechanism supporting the use of ascorbic acid supplementation for prevention of cataract progression.