The unusually high levels of saturation and thus order contribute to the uniqueness of human lens membranes. In addition, and unlike in most biomembranes, most of the lens lipids are associated with proteins, thus reducing their mobility. The major phospholipid of the human lens is dihydrosphingomyelin. Found in significant quantities only in primate lenses, particularly human ones, this lipid is so extremely stable that it was reported to be the only lipid remaining in a frozen mammoth 40,000 years after its death. Unusually high levels of cholesterol add peculiarity to the composition of lens membranes. Beyond the lateral segregation of lipids into dynamic domains known as rafts, the high abundance of cholesterol in the human lens leads to the formation of patches of pure cholesterol. Changes in human lens lipid composition with age and disease as well as differences among species are greater than those observed for any other biomembrane. The relationships among lens membrane composition, structure, and lipid conformation reviewed in this article are unique to the mammalian lens and offer exciting insights into lens membrane function. This review focuses on findings reported over the last two decades that demonstrate the uniqueness of mammalian lens membranes regarding their morphology and composition. Because the membranes of human lenses do undergo the most dramatic changes with age and cataractogenesis, the final sections of this review address our current knowledge of the unusual composition and organization of adult human lens membranes with and without opacification. Finally, the questions that still remain to be answered are presented.

Purpose: Meibomian gland dysfunction (MGD) is a common clinical problem that is often associated with evaporative dry eye disease. Alterations of the lipids of the meibomian glands have been identified in several studies of MGD. This prospective, observational, open-label clinical trial documents the improvement in both clinical signs and symptoms of disease as well as spectroscopic characteristics of the meibomian gland lipids after therapy with topical azithromycin ophthalmic solution and oral doxycycline treatment. Methods: Subjects with symptomatic MGD were recruited. Signs of MGD were evaluated with a slit lamp. Symptoms of MGD were measured by the response of subjects to a questionnaire. Meibum lipid–lipid interaction strength, conformation, and phase transition parameters, and meibum protein content were measured using Fourier transform infrared spectroscopy and principal component analysis. Terpenoids, short-chain CH₃ moieties, lipid oxidation, wax, cholesterylesters and glycerides were measured with a proton nuclear magnetic resonance (¹H-NMR) spectrometer. Results: Topical therapy with azithromycin and oral therapy with doxycycline relieved signs and symptoms and restored the lipid properties of the meibomian gland secretion toward normal. Compared with 4 weeks of azithromycin treatment reported in our previous study, oral doxycycline treatment was slightly less effective in improving foreign body sensation and the signs of plugging and secretion. In subjects with clinical evidence of MGD, changes in ordering of the lipids and phase transition temperature were brought closer to normal with azithromycin treatment than doxycycline treatment. Treatment with doxycycline but not azithromycin restored the Fourier transform infrared spectroscopy–principal component analysis scores and relative area of the ¹H-NMR resonance at 1.26 ppm. Both doxycycline and azithromycin treatment restored the levels of the relative areas of the ¹H-NMR resonance at 5.2 and 7.9 ppm to normal levels. The levels of meibum protein and meibum lipid oxidation were not influenced by azithromycin or doxycycline treatment. Conclusions: The mechanism of action of doxycycline may be different from that of azithromycin in therapy of MGD. It is notable that when carotenoids in meibum are low, as in MGD, the tear film is unstable and patients have the signs and symptoms of dry eyes. When carotenoids are restored with azithromycin and doxycycline treatment, tear film stability is restored and patients no longer have the signs and symptoms of dry eyes.

Purpose. 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. methods. 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 ³¹P-nuclear magnetic resonance spectroscopy. results. 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. conclusions. 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.

Purpose. Calcium is elevated in most cataractous human lenses and may contribute to cataractogenesis. In this study, age-related changes were examined in the total calcium content of clear human lenses and the binding of calcium to lens lipids and proteins. methods. Total lens calcium was determined by atomic absorption spectroscopy. Calcium binding was measured by light scattering and measurement of calcium by atomic absorption spectroscopy in bound and unbound fractions. results. The calcium content of clear human lenses decreased between 18 and 55 years of age and increased between 55 and 75 years, as well as in the presence of cataract. Total calcium levels in clear lenses from subjects with insulin-dependent diabetes did not differ from that in lenses of age-matched control subjects. In vitro binding studies have shown that lens lipids can bind nearly all the calcium present in the human lens. Age and cataract diminished the capacity of lens lipids to bind calcium. Calcium-induced light-scattering, measured in vitro for lens proteins, correlated with increasing age and cataract. conclusions. The data support the hypothesis that increased intracellular calcium concentrations and a diminished capacity of lens lipids to bind to calcium initiate a cascade of events that culminates in increased light-scattering from lipids and especially proteins. Calcium binding to lipid membranes cannot directly contribute to light-scattering in cataractous lenses. It has been suggested that most of the diffusible calcium in the lens is in the intercellular spaces and that lens lipids in the outer leaflet of the bilayer bind to that calcium. If so, this could account for the 150-fold difference between free and bound calcium levels in the lens.