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 白内障的确切机制尚不清楚，在那里 是令人信服的证据表明氧化损伤是 在这一过程中。铁催化氧化反应及其原因 对晶状体蛋白质、DNA和膜的损伤，类似于 根据白内障晶状体中发现的损坏类型进行分类。电熨斗 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。重要的是 最近的研究强调了铁蛋白对正常晶状体功能的影响 发现具有显性遗传性异常的人类 铁蛋白合成表现为早期双眼白内障。少年派找到了 晶状体上皮细胞合成铁蛋白，抗坏血酸 酸性和谷胱甘肽会增加铁蛋白浓度，而 过氧化氢会破坏氧化剂，减少铁蛋白的合成。 因此，她假设：在镜头中，铁约束 铁蛋白的能力是晶状体抗氧化剂的重要组成部分 潜力。抗坏血酸增加新铁蛋白的合成和 铁结合到这种蛋白质中，从而保护晶状体 免受氧化损伤。过氧化氢，除了直接 破坏晶状体细胞，降低晶状体抗氧化能力 铁蛋白合成减少。基于这一假设， 具体目标是确定依赖于时间和浓度的 抗坏血酸、谷胱甘肽、铁和过氧化氢的作用 铁蛋白合成、亚基组成、亚细胞 本地化，以及结合铁的能力。此外， 铁蛋白对晶状体上皮细胞的保护作用 氧化损伤将通过增加铁蛋白来确定 在这些细胞暴露于损害之前的浓度 过氧化氢的浓度。这些实验的结果将 提供有关铁蛋白和抗坏血酸作用的关键信息 酸性铁在晶状体中的新陈代谢，可能会提供一种特殊的 支持抗坏血酸使用的保护性生化机制 补充酸性物质以预防白内障进展。

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.