[Inhibition of cholesterol synthesis and cataract]

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.