Investigations on the presence of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-reductase, E.C.1.1.1.34) in lenses of various animal species.
The cholesterol requirements of the lens for the formation of plasma membranes are met by self-synthesis immediately after birth, this capacity, however, decreases considerably with increasing age, so that the deficit can only be met by exogenous supply. These findings are of great importance with respect to the qualitative assessment of extra-hepatical side effects of the substance class of HMG-CoA-reductase inhibitors on possible disturbances of lens transparency. In contrast to investigations of Mosley et al. (23) with rat and rabbit lenses, we did not find any activity of the HMG-CoA-reductase in our experiments with the lens cortex of calf, bovine, Beagle dog. The disturbances in lens transparency observed in chronical toxicity tests with high doses of HMG-CoA- reductase inhibitors might rather be due to the impairment of the exogenous cholesterol supply by a considerable decrease of the normal cholesterol level in the blood. The therapeutical treatment of pathologically increased blood cholesterol levels of patients should therefore not affect the transparency of human lenses. Relevant drug-safety-clinical studies confirm this experimentally substantiated supposition.
Kojima
M
M
Department of Experimental Ophthalmology, University of Bonn.
Hockwin
O
O
Rao
G S
GS
Garcia
J
J
D000818:Animals; D002417:Cattle; D004285:Dogs; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007908:Lens, Crystalline / Q000201:enzymology*; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D013045:Species Specificity
D006903:Hydroxymethylglutaryl CoA Reductases