PDF(Pubmed)
Abstract：
Clouding of the eye lens or cataract is an age-related anomaly that affects middle-aged humans. Exploration of the etiology points to a great extent to oxidative stress due to different forms of reactive oxygen species/metabolites such as Hydrogen peroxide (H2O2) that are generated due to intracellular metabolism and environmental factors like radiation. If accumulated and left unchecked, the imbalance between the production and degradation of H2O2 in the lens could lead to cataracts. Our objective was to explore ex vivo the effects of H2O2 on lens physiology. We investigated transparency, intracellular pH (pHi), intercellular gap junction coupling (GJC), hydrostatic pressure (HP) and membrane water permeability after subjecting two-month-old C57 wild-type (WT) mouse lenses for 3 h or 8 h in lens saline containing 50 μM H2O2; the results were compared with control lenses incubated in the saline without H2O2. There was a significant decrease in lens transparency in H2O2-treated lenses. In control lenses, pHi decreases from ∼7.34 in the surface fiber cells to 6.64 in the center. Experimental lenses exposed to H2O2 for 8 h showed a significant decrease in surface pH (from 7.34 to 6.86) and central pH (from 6.64 to 6.56), compared to the controls. There was a significant increase in GJC resistance in the differentiating (12-fold) and mature (1.4-fold) fiber cells compared to the control. Experimental lenses also showed a significant increase in HP which was ∼2-fold higher at the junction between the differentiating and mature fiber cells and ∼1.5-fold higher at the center compared to these locations in control lenses; HP at the surface was 0 mm Hg in either type lens. Fiber cell membrane water permeability significantly increased in H2O2-exposed lenses compared to controls. Our data demonstrate that elevated levels of lens intracellular H2O2 caused a decrease in intracellular pH and led to acidosis which most likely uncoupled GJs, and increased AQP0-dependent membrane water permeability causing a consequent rise in HP. We infer that an abnormal increase in intracellular H2O2 could induce acidosis, cause oxidative stress, alter lens microcirculation, and lead to the development of accelerated lens opacity and age-related cataracts.
摘要：
眼睛晶状体或白内障的浑浊是影响中年人的与年龄相关的异常。对病因学的探索在很大程度上指向由于细胞内代谢和环境因素如辐射而产生的不同形式的活性氧/代谢物如过氧化氢(H2O2)引起的氧化应激。如果累积并不检查，晶状体中H2O2的产生和降解之间的不平衡可能导致白内障。我们的目的是探索体外H2O2对晶状体生理的影响。我们调查了透明度，细胞内pH（pHi），细胞间缝隙结耦合（GJC），将两个月大的C57野生型（WT）小鼠晶状体在含有50μMH2O2的晶状体盐水中放置3小时或8小时后，静水压力（HP）和膜水渗透性；将结果与在不含H2O2的盐水中孵育的对照镜片进行比较。在H2O2处理的镜片中,镜片透明度显著降低。在控制镜头中，pHi从表面纤维细胞的~7.34下降到中心的6.64。实验镜片暴露于H2O28小时显示表面pH值（从7.34到6.86）和中心pH值（从6.64到6.56）显著降低，与对照组相比。与对照相比,分化(12倍)和成熟(1.4倍)纤维细胞中的GJC抗性显著增加。实验镜片也显示出HP的显着增加，与对照镜片中的这些位置相比，分化和成熟纤维细胞之间的交界处的HP高出约2倍，中心处的HP高出约1.5倍；两种类型的镜片中表面的HP均为0mmHg。与对照组相比，暴露于H2O2的镜片中的纤维细胞膜水渗透性显着增加。我们的数据表明，晶状体细胞内H2O2水平升高导致细胞内pH值降低，并导致酸中毒，这很可能使GJs分离。并增加了依赖AQP0的膜水渗透率，从而导致HP升高。我们推断细胞内H2O2的异常增加可以诱导酸中毒，引起氧化应激，改变晶状体微循环，并导致加速晶状体混浊和年龄相关性白内障的发展。
