Substantial Changes in the Phospholipid Content of Human Lenses With Age and Cataract

Abstract

Abstract: : Purpose: ³¹P–Nuclear magnetic resonance spectroscopy can be used to quantify phospholipids that are either undetectable or unresolvable by standard protocols. The purpose of this study was to investigate lens phospholipid composition with age and cataract using this technique. Methods: Lipids were extracted from individual and pooled human lenses of similar age or cataract classification (mature nuclear, mature mixed cortical and nuclear, immature posterior subcapsular cataracts. ³¹P–Nuclear magnetic resonance spectroscopy and gravimetric analysis were used to quantify lipids. Results: In clear lenses, the relative amount of one of the PE–related lipids decreased from 33% at 10 years of age to 8% at 50 years of age. The relative amount of sphingolipid increased from 30% to 60% over the same age range. The relative change is exacerbated with cataract. With cataract, PE–related lipids were undetectable and the relative amount of sphingolipid increased to 80%. Concomitant with these changes in phospholipid composition, the total amount of lipid decreased by over 30% with cataract. The cataract–related decrease in glycerolipids were 89%, more than twice greater than the decrease in sphingolipid (38%). Conclusions: Lens glycerolipids like phosphatidylcholine are three times as unsaturated as lens sphingolipid. Lipids with more double bonds like phosphatidylcholine are selectively oxidized over lipids with fewer double bonds, like sphingolipids, because the rate constant for the propagation step sharply increases when the number of lipid double bonds is increased. We believe that selective oxidation of unsaturated lipids could be the initial event leading to the decrease in lens glycerolipids that results in a relative enrichment in lens sphingolipid, and thus a more saturated lipid bilayer. The lens lipid changes with age and cataract are substantial, greater than the changes in lipid levels reported for any organ or disease. As a result of these lens lipid alterations, our studies show that light scattering increases, calcium pump activity is reduced, protein–lipid interactions change, and fiber cell elongation may slow. The alterations have important implications with respect to aging and lifespan research in the lens and other tissues.

Keywords: cataract • lipids • aging