Hockwin O, Kojima M, Czubayko F, von Bergmann K
Abteilung für experimentelle Ophthalmologie, Medizinische Einrichtungen der Universität, Bonn, Bundesrepublik Deutschland.
Fortschr Ophthalmol. 1991;88(4):393-5.
The cholesterol requirements of the lens for the formation of plasma membranes are met by self-synthesis only until early postnatal life. This ability subsequently decreases with increasing age and probably ceases altogether. The cholesterol supply then has to come from exogenous sources. These findings are of great importance for the qualitative assessment of extrahepatic side effects of HMG-CoA-reductase inhibitors given for disturbances of lens transparency. The observation of cataracts in chronic toxicity tests with high doses in beagle dogs suggested that the lens enzyme was also affected by the inhibitor, thus causing cataracts. In contrast to other workers' results, we did not find any activity of HMG-CoA-reductase in our experiments with calf, bovine, dog and rat lenses. Preliminary studies with bovine eyes demonstrate a direct correlation between the cholesterol serum level and the content of the aqueous humor. This shows the importance of the exogenous supply for the lens requirements. A further strong argument is that the use of HMG-CoA-reductase inhibitors in patients with pathologically increased cholesterol level is safe as far as the lens transparency is concerned, as demonstrated in clinical trials.
晶状体质膜形成所需的胆固醇仅在出生后早期由自身合成满足。随着年龄增长,这种能力随后下降,可能完全停止。此后胆固醇供应必须来自外源。这些发现对于定性评估因晶状体透明度受损而给予的HMG-CoA还原酶抑制剂的肝外副作用非常重要。在比格犬高剂量慢性毒性试验中观察到白内障,提示晶状体酶也受到抑制剂影响,从而导致白内障。与其他研究人员的结果不同,我们在对小牛、牛、狗和大鼠晶状体的实验中未发现HMG-CoA还原酶的任何活性。对牛眼的初步研究表明血清胆固醇水平与房水含量之间存在直接相关性。这表明外源供应对晶状体需求的重要性。另一个有力论据是,如临床试验所示,就晶状体透明度而言,在胆固醇水平病理性升高的患者中使用HMG-CoA还原酶抑制剂是安全的。