NUCLEAR CATARACT: ROLE OF UV FILTERS AND THE LENS BARRIER

描述：核性白内障（ARM）是世界失明的主要原因。在过去的几年里，我们对ARN白内障的理解发生了革命性的变化。直到那时，基本上所有已知的是ARN白内障与透镜蛋白的深度氧化、不溶解、着色和交联有关。目前还不清楚为什么这些晶状体的细胞核会发生这种氧化变化。最近的进展表明，ARN白内障的发展是透镜随年龄变化的直接结果。（其中包括发现透镜着色的原因，以及允许透镜中心发生氧化的生化/物理基础;最终导致白内障。）简单地说，抗氧化剂谷胱甘肽从皮质中合成或还原的部位进入透镜核的运动障碍在老年人中形成。因此，老年正常人透镜的核变得对氧化应激敏感。这些发现表明，ARN白内障的大部分（如果不是全部）特征可以根据中年时透镜屏障的发病以及随后的核蛋白与活性分子（如紫外线过滤剂）的氧化和反应来解释。我们建议调查的原因，发病的障碍，在中年。2004年12月，我们发现正常晶状体的核随着年龄的增长硬度会大幅增加。难道这就是结界形成的原因？本补助金申请的目的是调查这一建议。如果得到证实，这将对未来的白内障治疗产生重大影响，因为它提供了药物干预可能预防或延迟ARN白内障的希望。由于透镜核在调节时必须经历形状的重大变化，因此了解这种巨大硬化的分子基础也可能影响我们对老花眼的理解。

DESCRIPTION: Age-related nuclear (ARM) cataract is a major cause of world blindness. There has been a revolution in our understanding of ARN cataract in the past few years. Up until that time, essentially all that was known was that ARN cataract was associated with profound oxidation, insolubilization, coloration and cross-linking of lens proteins. It was unclear why such oxidative changes occurred in the nuclei of these lenses. Recent advances suggest that ARN cataract develops as a direct result of changes in the lens that occur with age. (These include the discovery of a reason for lens coloration and also the biochemical/physical basis that allows oxidation in the centre of the lens to proceed; resulting ultimately in cataract.) Briefly, a barrier to the movement of the antioxidant, glutathione from its site of synthesis or reduction in the cortex, into the lens nucleus, forms in older individuals. Thus the nucleus of the older normal human lens becomes susceptible to oxidative stress. These findings suggest that most, if not all, of the features of ARN cataract may be explained on the basis of the onset of the lens barrier in middle age and the subsequent oxidation and reaction of the nuclear proteins with reactive molecules, such as UV filters. We propose to investigate the reason for the onset of the barrier at middle age. In December 2004 we showed that the nucleus of normal lenses undergoes a massive increase in hardness with age. Could this be the reason for the development of the barrier? It is the aim of this grant application to investigate this proposal. If confirmed, this would have major implications for future cataract treatment, since it offers hope that drug intervention may be possible to prevent, or delay, ARN cataract. Since the lens nucleus must undergo a major change in shape on accommodation, understanding the molecular basis of this enormous hardening may also impact on our understanding of presbyopia.