Human lens cholesterol concentrations in patients who used lovastatin or simvastatin

Objective: To determine whether long-term therapeutic use of the hypocholes terolemic drugs lovastatin and simvastatin significantly alters the distrib ution and concentration of cholesterol in the human lens. Such changes migh t precede observable alterations in lens structure. Methods: Pairs of lenses (9-13 pairs) from patients (age range, 46-81 years ) who had been taking lovastatin or simvastatin before their death (estimat ed for the previous 2-4 years) and lenses from similarly aged control subje cts were divided into outer cortex and inner cortex plus nucleus by dissolu tion in a detergent-containing buffer. Ten minutes of dissolution removed 1 7% to 19% of the lens to tal volume, which accounted for about 20% of the w idth of the equatorial cortex and 75% of the width of the sagittal cortex. This fraction plus the residual lens was homogenized, saponified, and assay ed for cholesterol by gas-liquid chromatography. Results: The cortex of adult control lenses contained about 4 mu g of chole sterol per cubic millimeter of volume. This concentration increased to 10 t o 15 mu g/mm(3) in the adult nucleus and decreased to about 6 mu g/mm(3) in the juvenile and fetal nucleus. Treatment with neither lovastatin nor simv astatin significantly altered the concentration of cholesterol in either th e cortex or nuclear fractions. Conclusions: Variations in concentration of cholesterol along the radii of the lens reflect differences in the density or packing of fiber cell membra nes. The observed distribution of cholesterol supports the recent model of the adult lens structure, which, from surface to center, is the cortex, adu lt nucleus,juvenile nucleus, fetal nucleus, and embryonic nucleus. Finding no significant changes in concentration of cholesterol in the cortex formed during treatment with lovastatin or simvastatin reinforces the results of clinical studies chat indicate a high lenticular safety of 3-hydroxy-3-meth ylglutaryl coenzyme A reductase inhibitors. Nevertheless, caution is encour aged in assuming a similar ocular safety in newer drugs that inhibit choles terol synthesis at later metabolic steps. Clinical Relevance: Does clinical use of hypocholesterolemic drugs alter le ns cholesterol?