NUCLEAR CATARACT: ROLE OF UV FILTERS AND THE LENS BARRIER

描述：老年性核性(臂)白内障是导致世界失明的主要原因。在过去的几年里，我们对ARN白内障的认识发生了一场革命。在那之前，基本上我们所知道的就是ARN白内障与晶状体蛋白质的深度氧化、不溶解、着色和交联性有关。目前还不清楚为什么这些晶状体的细胞核会发生这样的氧化变化。最近的进展表明，ARN白内障的发展是随着年龄的增长晶状体发生变化的直接结果。(包括发现晶状体变色的原因，以及允许晶状体中心氧化进行的生化/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合成或还原的位置进入晶状体核的障碍在老年人身上形成。因此，年龄较大的正常人晶状体的细胞核对氧化应激很敏感。这些发现表明，ARN白内障的大部分(如果不是全部)特征可能是基于中年时晶状体屏障的开始以及随后核蛋白与活性分子(如紫外线过滤器)的氧化和反应来解释的。我们建议调查这一障碍在中年出现的原因。2004年12月，我们发现随着年龄的增长，正常晶状体的核经历了大量的硬度增加。这可能是障碍发展的原因吗？这项拨款申请的目的是调查这项建议。如果得到证实，这将对未来的白内障治疗产生重大影响，因为它带来了药物干预可能预防或推迟ARN白内障的希望。由于晶状体核在调节时必须经历重大的形状变化，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.