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Laxman Mainali, Marija Raguz, William J O'Brien, Witold Karol Subczynski, ; Age-dependent changes in the organization of cholesterol in membranes derived from the total lipids extracted from the human lens cortex and nucleus. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5578.
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© ARVO (1962-2015); The Authors (2016-present)
Understanding of the physiological functions of cholesterol (Chol) requires studies of Chol functions at the molecular level. Chol-induced changes in the structure and properties of lipid-bilayer membranes can be investigated by modeling the lipid-bilayer portion of fiber-cell plasma membranes. In these studies we investigated its interactions in model membranes made from the total lipid extracts from eye lenses from human donors of different age groups (0-20, 21-40, 41-60 and 61-70 year old).
The conventional electron paramagnetic resonance (EPR) was used to investigate the alkyl chain order and hydrophobicity of membrane interior, while the saturation-recovery EPR to study alkyl chain fluidity and oxygen transport within the lipid bilayer. The differential scanning calorimetry (DSC) was used to detect the formation of Chol crystals.
The Chol/phospholipd (Chol/PL) molar ratio in lipids extracted from cortex was 0.63, 1.01, 1.38, and 1.80 and from nucleus 0.71, 1.21, 2.1, and 4.4, respectively, for groups 0-20, 21-40, 41-60, and 61-70 year old donors. For the youngest donors, the cortical and nuclear lipid bilayers formed homogeneous PL-Chol domains (PCD) saturated (or almost saturated) with Chol. All membranes made of lipids from other age groups contained the pure Chol bilayer domain (CBD) immersed into the PCD. The size/amount of the CBD was found to increase with age in both cortical and nuclear membranes. In nuclear membranes from the group of 61-70 year old donors, exhibiting the highest Chol/PL molar ratio of 4.4, additionally Chol crystals were detected.
The PL composition of the human eye-lens membranes changes with age and region of the lens. The change of the Chol content in fiber-cell membranes occurring with age manifests itself by an increase of the total Chol/PL molar ratio as well as a higher Chol/PL molar ratio in nucleus relative to the cortex. Independently of the age-dependent changes of the PL composition the properties of the PCD are age-independent. We hypothesize that high, saturating Chol content keeps these properties constant and independent of the PL composition. Additional we theorize that high Chol content is necessary to maintain the membrane and fiber cell homeostasis and thus protect against cataract formation.
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