Spector A, Wang G M, Wang R R, Garner W H, Moll H
Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Curr Eye Res. 1993 Feb;12(2):163-79. doi: 10.3109/02713689308999484.
H2O2 stress is shown to produce cataract in cultured rat lenses. The loss of transparency begins in the equatorial region within 24 hours and the entire superficial cortex is opaque by 96 hours. No involvement of the nuclear region is observed. However after an additional 48 hours, the nuclear region becomes opaque. The loss of transparency is accompanied by a large uptake of H2O which occurs gradually over the 96 hour period, complete loss of glyceraldehyde phosphate dehydrogenase (GPD) activity, almost complete loss of non-protein thiol and a slight decrease in protein thiol. Control lenses show no change other than the establishment of a new non-protein thiol base line approximately 60% lower than 0 time levels. The Alcon glutathione peroxidase type mimic, AL-3823A, completely eliminates almost all of the H2O2 induced effects and the lens remains transparent. Utilizing a more severe photochemical model than may be anticipated physiologically with 10 microM riboflavin and exposure to daylight fluorescent lamps, significant concentrations of superoxide and low levels of OH. are produced as well as extraordinarily high concentrations of H2O2 ranging from about 400 to 1000 microM. As with the H2O2 model, opacification begins at the equator but the cataract develops more rapidly, the lens being completely opaque by 68 hours. Hydration, GPD activity, non-protein and protein thiol all decrease more rapidly than in the H2O2 model. AL-3823A prevents loss of transparency until approximately 92 hours and markedly decreases changes in other parameters. At 92 hours, slight loss of transparency is observed. Catalase is somewhat less effective. AL-3823A is shown to also significantly decrease superoxide levels. The marked delay in the onset of changes in lens biochemistry and physiology in the severe photochemical stress model and the maintenance of normal parameters in the H2O2 model in the presence of AL-3823A suggests that such compounds may prevent cataract caused by oxidative stress under physiological conditions.
已证实过氧化氢（H2O2）应激会在培养的大鼠晶状体中引发白内障。透明度的丧失在24小时内始于赤道区域，到96小时时整个表层皮质变得不透明。未观察到核区域受到影响。然而，再过48小时后，核区域也变得不透明。透明度的丧失伴随着大量水分的摄取，这种摄取在96小时内逐渐发生，同时磷酸甘油醛脱氢酶（GPD）活性完全丧失，非蛋白巯基几乎完全丧失，蛋白巯基略有减少。对照晶状体除了建立了一个比0小时水平低约60%的新的非蛋白巯基基线外，没有其他变化。爱尔康谷胱甘肽过氧化物酶型模拟物AL - 3823A几乎完全消除了所有由H2O2诱导的效应，晶状体保持透明。使用一种比生理预期更严重的光化学模型，即10微摩尔核黄素并暴露于日光荧光灯下，会产生高浓度的超氧化物和低水平的羟基自由基（OH.），以及范围约为400至1000微摩尔的极高浓度的H2O2。与H2O2模型一样，浑浊从赤道开始，但白内障发展得更快，到68小时时晶状体完全不透明。水合作用、GPD活性、非蛋白和蛋白巯基的下降都比H2O2模型中更快。AL - 3823A可防止透明度丧失至约92小时，并显著减少其他参数的变化。在92小时时，观察到轻微的透明度丧失。过氧化氢酶的效果稍差。AL - 3823A还被证明能显著降低超氧化物水平。在严重光化学应激模型中晶状体生物化学和生理学变化的显著延迟以及在AL - 3823A存在下H2O2模型中正常参数的维持表明，这类化合物可能在生理条件下预防由氧化应激引起的白内障。
