ACTIVATION OF THE HEXOSE MONOPHOSPHATE SHUNT IN THE LENS

现在已经知道，人类老年性白内障经历了广泛的 氧化蚀变。这一点从以下几个方面得到了证明 白内障中富含二硫化物的高分子量蛋白质聚集体 隐形眼镜。氧化的来源尚未确定。 然而，在房水中发现了升高的过氧化氢水平。 以及人类白内障患者的晶状体。这表明，过氧化氢及其 衍生物可能参与了白内障的发生和白内障的发生 不能有效地解毒过氧化氢。我们建议调查： (1)晶状体的过氧化氢解毒功能是否存在先天弱点 机制，(2)是否存在与年龄相关的H_2O_2解毒丧失， 尤其是己糖单磷酸分流偶联体系，(3)是否 可以确定过氧化氢引起的损伤，以及(4)是否有可能 增强晶状体对过氧化氢的抵抗力。生化分析和核检测 核磁共振光谱学将在这项提议中使用。 圆满完成拟议的研究和演示 可行性将使我们能够为老年人开发抗白内障药剂(S) 人类老年性白内障的治疗。

It is now known that human senile cataracts have undergone extensive oxidative alteration. This is evidenced by the accumulation of disulfide-rich high molecular weight protein aggregates in the cataractous lenses. The source of oxidation has not yet been definitively identified. Elevated H2O2 levels, however, have been discovered in the aqueous humor and the lens of human cataract patients. This suggests that H2O2 and its derivatives may be involved in the cataractogenesis and that the cataracts are incapable of detoxifying H2O2 efficiently. We propose to investigate: (1) whether there is an inherent weakness in the lens's H2O2 detoxifying mechanism, (2) whether there is an age-related loss of H2O2 detoxification, particularly the hexose monophosphate shunt-coupled system, (3) whether H2O2-induced damage can be identified, and (4) whether it is possible to augment the lens's resistance to H2O2. Both biochemical assays and nuclear magnetic resonance spectroscopy will be employed in this proposal. Successful completion of the proposed studies and demonstration of feasibility will enable us to develop anti-cataract agent(s) for the treatment of human senile cataracts.