Cheng H M, Fagerholm P, Chylack L T
Exp Eye Res. 1983 Jul;37(1):11-21. doi: 10.1016/0014-4835(83)90145-8.
Both aldose reductase and glutathione reductase share a common cofactor, NADPH. Glutathione reductase is preferentially activated due to its higher affinity for the cofactor. Since NADPH is primarily consumed by glutathione reductase, which in conjunction with glutathione peroxidase detoxifies H2O2 present in the aqueous humor, the cataractogenic role of sorbitol-induced osmotic pressure must therefore depend on the availability of NADPH for aldose reductase activity. We examined the response of the lens to an oxidative-osmotic double stress and found that the lens indeed produced 79% less sorbitol and 45% less fructose than a lens subjected to the osmotic stress alone. Morphological studies showed that photo-oxidation damaged the epithelium where the cation pump resided. However, with additional osmotic stress, the swelling of lens fibers in the posterior pole region became more pronounced, and cell nuclei deep in the lens nuclear bow were dislodged to the posterior pole. This could be explained by the slight but significant loss of K+ in the lenses under the double stress. Apparently, the slightly decreased 86Rb uptake (26% loss), caused by photooxidation could not maintain adequate ionic balance even though the stress from accumulation of sorbitol + fructose was sub-maximal. No disturbance in the glycolytic activity or to the 86Rb efflux was found in these lenses, however.
醛糖还原酶和谷胱甘肽还原酶都共用一种辅助因子，即还原型辅酶Ⅱ（NADPH）。由于谷胱甘肽还原酶对该辅助因子具有更高的亲和力，因此它被优先激活。由于NADPH主要被谷胱甘肽还原酶消耗，谷胱甘肽还原酶与谷胱甘肽过氧化物酶共同作用可清除房水中存在的过氧化氢，所以山梨醇诱导的渗透压的致白内障作用必然取决于NADPH对醛糖还原酶活性的可用性。我们研究了晶状体对氧化 - 渗透双重应激的反应，发现与仅受到渗透应激的晶状体相比，该晶状体产生的山梨醇确实减少了79%，果糖减少了45%。形态学研究表明，光氧化损伤了阳离子泵所在的上皮细胞。然而，在额外的渗透应激下，晶状体后极区域纤维的肿胀变得更加明显，晶状体核弓深处的细胞核被挤到了后极。这可以通过双重应激下晶状体中钾离子轻微但显著的流失来解释。显然，光氧化导致的86Rb摄取略有下降（损失26%），即使山梨醇 + 果糖积累产生的应激未达到最大值，也无法维持足够的离子平衡。然而，在这些晶状体中未发现糖酵解活性或86Rb外流受到干扰。
