The molecular processes involved in age-related human nuclear cataract

该项目旨在了解与年龄相关的核性白内障的分子基础，特别是我们的紫外线过滤化合物的作用。通过了解白内障的发生机制，我们希望能够开发出干预这一过程的方法，从而预防或至少延缓白内障的发生。将进行实验，以确定最具活性的紫外线滤光剂3-羟基犬尿氨酸与从不同年龄的正常人类晶状体和白内障晶状体中分离出来的晶状体蛋白（晶体蛋白）的共价结合程度。此外，还将研究犬尿氨酸、3-羟基犬尿氨酸和3-羟基犬尿氨酸糖苷在模型体系中修饰的晶状体结晶蛋白的性质。这将包括检查紫外滤光器修饰对结晶蛋白暴露在紫外线下后蛋白质自由基形成的影响，以及对蛋白质结合的紫外滤光器作为金属络合和化学还原位点的假设的调查。众所周知，白内障与氧化有关，还将进行实验，测量晶状体核中的氧气浓度，以便模型研究更准确地反映晶状体内的情况，并观察氧气水平是否可能影响白内障的发病。

This project seeks to understand the molecular basis for age-related nuclear cataract, and in particular the role of our UV filter compounds. By gaining an understanding of the mechanism of cataract we hope to be able to develop ways to interfere with the process and thus prevent, or at least delay, human cataract. Experiments will be undertaken to determine the extent of covalent binding of the most reactive UV filter, 3-hydroxykynurenine, to lens proteins (crystallins) isolated from normal human lenses of various ages, and from cataract lenses. In addition, the properties of lens crystallins that have been modified in model systems by kynurenine, 3-hydroxykynurenine and 3-hydroxykynurenine glucoside will be investigated. This will include examination of the impact of the UV filter modifications on the formation of protein radicals following exposure of the crystallins to UV light and an investigation of the hypothesis that the protein-bound UV filters act as sites for both complexing of metals and their chemical reduction. Oxidation is known to be involved in cataract and experiments will also be undertaken to measure the concentration of oxygen in the lens nucleus, so that the model studies more accurately reflect conditions within the lens, and to see if the levels of oxygen may inflluence the onset of cataract.