Abstract
Purpose :
The most unique biochemical characteristic of the eye lens fiber cell plasma membrane is its extremely high cholesterol content. The cholesterol/phospholipid molar ratio of the human fiber cell membrane ranges from 1 to 2 in the cortex and can be as high as 3 to 4 in the lens nucleus. The need for such a high cholesterol content in the lens is still unclear. It is evident, however, that the disturbance of cholesterol homeostasis may result in damages associated with cataracts.
Methods :
Results presented here were obtained using electron paramagnetic resonance spin-labeling methods to discriminate cholesterol bilayer domains (CBDs), and differential scanning calorimetry to discriminate cholesterol crystals. Investigated lipid bilayer membranes were prepared from commercially available lipids and total lipids extracted from clear and cataractous human lens cortexes and nuclei as well as from the eyes of different animals. In key experiments, membranes were prepared using a rapid solvent exchange method.
Results :
The extremely high (saturating) content of cholesterol in the fiber-cell membrane keeps the bulk physical properties of the lipid-bilayer portion of the membrane consistent and independent of changes in the phospholipid composition. The CBD provides buffering capacity for cholesterol concentration in the surrounding phospholipid bilayer, keeping it at a constant level of saturation. The high cholesterol content in fiber-cell plasma membranes ensures that the lipid bilayer portion of these membranes forms the high hydrophobic barrier for permeation of polar molecules. The lipid bilayer portion of lens membranes, with its unique lipid composition and structure, forms significant barriers to oxygen transport into the lens interior.
Conclusions :
The presence of CBDs seems to play an integral role in the regulation of cholesterol-dependent processes in fiber cell membranes and in the maintenance of fiber cell membrane homeostasis. Obtained results suggest that the high cholesterol content, formation of CBDs, and formation of cholesterol crystals should not be considered as major predispositions for the development of age-related cataracts.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.