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M. Raguz, W. K. Subczynski; The Crucial Role of Cholesterol in Maintaining Lens Membrane Homeostasis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4377.
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© ARVO (1962-2015); The Authors (2016-present)
The lipid composition of the lens fiber cell membrane is significantly different between species, and changes as both animals and humans age. Usually, such notable change would result in the alteration of the membrane’s physical properties, which would affect the function of proteins immersed in the lipid bilayer. We hypothesize that the extremely high content of cholesterol in the fiber cell plasma membrane keeps the bulk physical properties of the lipid bilayer membrane consistent and independent of changes in the phospholipid composition.
The physical properties of membranes, including profiles of the alkyl chain order, fluidity, hydrophobicity, and oxygen transport parameter (oxygen diffusion-concentration product), were investigated using conventional and pulse electron paramagnetic resonance spin-labeling methods. These methods provide a unique opportunity to discriminate coexisting membrane domains.
The physical properties of membranes derived from the total lipid extract of six-month-old calf and pig lenses, and those derived from the cortical and nuclear lipid extracts of a two-year-old-cow lens, were investigated and compared with the properties of membranes made of representative phospholipids with and without saturating amounts of cholesterol. Surprisingly, the physical properties of the bulk phospholipid-cholesterol domain were nearly the same in all of the investigated membranes and were very similar to the properties of phospholipid membranes saturated with cholesterol. However, they differed drastically from the properties of pure phospholipid membranes (without cholesterol). In membranes made of the nuclear cow-lens lipids and pig-lens lipids additionally enriched with cholesterol, the cholesterol crystalline domain was detected. The presence of this domain does not affect the bulk properties of the surrounding phospholipid-cholesterol domain. The estimated oxygen permeability coefficient across the cholesterol crystalline domain was significantly lower than across the water layer of the same thickness and the bulk phospholipid-cholesterol domain.
The cholesterol crystalline domain, being the integral part of the aged lens membrane, provides buffering capacity for the cholesterol concentration in the surrounding phospholipid bilayer, keeping it at a constant saturating level and thus keeping physical properties of the membrane consistent and independent of changes in the phospholipid composition. The presence of this domain, which significantly reduces oxygen transport in the lens, should also help to maintain lens transparency to visible light.
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