Human Lens Phospholipid Changes with Age and Cataract

To determine the phospholipid changes responsible for the increase in membrane lipid hydrocarbon chain order, or stiffness, with age and cataract in the human lens.Clear human lenses were pooled into four groups, with donors ranging in age from 15 to 29, 30 to 49, 50 to 64, and 65 to 74 years. Whole human cataractous lenses were obtained from donors after extracapsular cataract extraction. Cataractous lenses were grouped into four classifications: mature, mixed cortical and nuclear, immature nuclear sclerotic, mature posterior subcapsular, and mature nuclear. Lipids were extracted and quantified gravimetrically. The relative phospholipid composition was determined by (31)P-nuclear magnetic resonance spectroscopy.The relative and absolute amount of sphingolipids, including dihydrosphingomyelin and sphingomyelin, increased with age, whereas glycerolipids, including phosphatidylcholine and two phosphatidylethanolamine-related phospholipids, decreased. These changes were exacerbated by the presence of cataract and were substantial, greater than the changes in lipid levels reported in any organ in association with any disease.The changes in the amount of lipids with age and cataract support the idea that glycerolipids are selectively oxidized over lipids with fewer double bonds, such as sphingolipids. As a result of the elevation of sphingolipid levels with species, age, and cataract, lipid hydrocarbon chain order, or stiffness, increases. Increased membrane stiffness may increase light-scattering, reduce calcium pump activity, alter protein-lipid interactions, and perhaps slow fiber cell elongation.