Heys Karl R, Friedrich Michael G, Truscott Roger J W
Save Sight Institute, University of Sydney, Sydney, NSW 2001, Australia.
Aging Cell. 2007 Dec;6(6):807-15. doi: 10.1111/j.1474-9726.2007.00342.x. Epub 2007 Oct 30.
Presbyopia, the inability to focus up close, affects everyone by age 50 and is the most common eye condition. It is thought to result from changes to the lens over time making it less flexible. We present evidence that presbyopia may be the result of age-related changes to the proteins of the lens fibre cells. Specifically, we show that there is a progressive decrease in the concentration of the chaperone, alpha-crystallin, in human lens nuclei with age, as it becomes incorporated into high molecular weight aggregates and insoluble protein. This is accompanied by a large increase in lens stiffness. Stiffness increases even more dramatically after middle age following the disappearance of free soluble alpha-crystallin from the centre of the lens. These alterations in alpha-crystallin and aggregated protein in human lenses can be reproduced simply by exposing intact pig lenses to elevated temperatures, for example, 50 degrees C. In this model system, the same protein changes are also associated with a progressive increase in lens stiffness. These data suggest a functional role for alpha-crystallin in the human lens acting as a small heat shock protein and helping to maintain lens flexibility. Presbyopia may be the result of a loss of alpha-crystallin coupled with progressive heat-induced denaturation of structural proteins in the lens during the first five decades of life.
老花眼，即无法聚焦近距离物体，到50岁时每个人都会受到影响，是最常见的眼部疾病。人们认为它是由于晶状体随时间变化而变得不那么灵活所致。我们提供的证据表明，老花眼可能是晶状体纤维细胞蛋白质随年龄变化的结果。具体而言，我们发现随着年龄增长，人晶状体核中伴侣蛋白α-晶体蛋白的浓度逐渐降低，因为它会形成高分子量聚集体和不溶性蛋白质。这伴随着晶状体硬度的大幅增加。中年以后，随着晶状体中心游离可溶性α-晶体蛋白的消失，硬度增加得更为显著。通过将完整的猪晶状体暴露在高温下，例如50摄氏度，就可以再现人晶状体中α-晶体蛋白和聚集蛋白的这些变化。在这个模型系统中，相同的蛋白质变化也与晶状体硬度的逐渐增加有关。这些数据表明α-晶体蛋白在人晶状体中起着功能性作用，作为一种小热休克蛋白，有助于维持晶状体的柔韧性。老花眼可能是由于在生命的前五十 年中α-晶体蛋白的丧失以及晶状体中结构蛋白逐渐受热诱导变性所致。
