Langford-Smith Alex, Tilakaratna Viranga, Lythgoe Paul R, Clark Simon J, Bishop Paul N, Day Anthony J
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
School of Earth, Atmospheric and Environmental Sciences and Williamson Research Centre for Molecular Environmental Science, University of Manchester, Manchester, United Kingdom.
PLoS One. 2016 Jan 21;11(1):e0147576. doi: 10.1371/journal.pone.0147576. eCollection 2016.
Age-related cataract formation is the primary cause of blindness worldwide and although treatable by surgical removal of the lens the majority of sufferers have neither the finances nor access to the medical facilities required. Therefore, a better understanding of the pathogenesis of cataract may identify new therapeutic targets to prevent or slow its progression. Cataract incidence is strongly correlated with age and cigarette smoking, factors that are often associated with accumulation of metal ions in other tissues. Therefore this study evaluated the age-related changes in 14 metal ions in 32 post mortem human lenses without known cataract from donors of 11 to 82 years of age by inductively coupled plasma mass spectrometry; smoking-related changes in 10 smokers verses 14 non-smokers were also analysed. A significant age-related increase in selenium and decrease in copper ions was observed for the first time in the lens tissue, where cadmium ion levels were also increased as has been seen previously. Aluminium and vanadium ions were found to be increased in smokers compared to non-smokers (an analysis that has only been carried out before in lenses with cataract). These changes in metal ions, i.e. that occur as a consequence of normal ageing and of smoking, could contribute to cataract formation via induction of oxidative stress pathways, modulation of extracellular matrix structure/function and cellular toxicity. Thus, this study has identified novel changes in metal ions in human lens that could potentially drive the pathology of cataract formation.
年龄相关性白内障的形成是全球失明的主要原因,尽管通过手术摘除晶状体可进行治疗,但大多数患者既没有资金也无法获得所需的医疗设施。因此,更好地了解白内障的发病机制可能会确定新的治疗靶点,以预防或减缓其进展。白内障的发病率与年龄和吸烟密切相关,而这些因素通常与其他组织中金属离子的积累有关。因此,本研究通过电感耦合等离子体质谱法评估了11至82岁供体的32个无已知白内障的死后人类晶状体中14种金属离子的年龄相关变化;还分析了10名吸烟者与14名非吸烟者之间与吸烟相关的变化。首次在晶状体组织中观察到硒随年龄显著增加,铜离子减少,镉离子水平也如先前所见有所增加。与非吸烟者相比,吸烟者体内的铝和钒离子增加(此前仅在患有白内障的晶状体中进行过此类分析)。这些金属离子的变化,即正常衰老和吸烟导致的变化,可能通过诱导氧化应激途径、调节细胞外基质结构/功能和细胞毒性而导致白内障形成。因此,本研究确定了人类晶状体中金属离子的新变化,这些变化可能潜在地推动白内障形成的病理过程。