Functions of Cholesterol and the Cholesterol Bilayer Domain Specific to the Fiber-Cell Plasma Membrane of the Eye Lens

Abstract

The most unique feature of the eye lens fiber-cell plasma membrane is its extremely high cholesterol content. Cholesterol saturates the bulk phospholipid bilayer and induces formation of immiscible cholesterol bilayer domains (CBDs) within the membrane. Our results (based on EPR spin-labeling experiments with lens-lipid membranes), along with a literature search, have allowed us to identify the significant functions of cholesterol specific to the fiber-cell plasma membrane, which are manifest through cholesterol-membrane interactions. The crucial role is played by the CBD. The presence of the CBD ensures that the surrounding phospholipid bilayer is saturated with cholesterol. The saturating cholesterol content in fiber-cell membranes keeps the bulk physical properties of lens-lipid membranes consistent and independent of changes in phospholipid composition. Thus, the CBD helps to maintain lens-membrane homeostasis when the membrane phospholipid composition changes significantly. The CBD raises the barrier for oxygen transport across the fiber-cell membrane, which should help to maintain a low oxygen concentration in the lens interior. It is hypothesized that the appearance of the CBD in the fiber-cell membrane is controlled by the phospholipid composition of the membrane. Saturation with cholesterol smoothes the phospholipid-bilayer surface, which should decrease light scattering and help to maintain lens transparency. Other functions of cholesterol include formation of hydrophobic and rigidity barriers across the bulk phospholipid-cholesterol domain and formation of hydrophobic channels in the central region of the membrane for transport of small, nonpolar molecules parallel to the membrane surface. In this review, we will provide data supporting these hypotheses.

Properties of membranes derived from the total lipids extracted from clear and cataractous lenses of 61–70-year-old human donors

“…We have investigated membranes with lipid compositions resembling those of the eye lenses of different species (Mainali et al 2012a, 2013b; Raguz et al 2009) and lens-lipid membranes formed from lipids extracted from the eyes of different species, donors of different age, and different regions of the eye lens (Mainali et al 2012a, 2013b; Raguz et al 2008, 2009; Widomska et al 2007). Previous research, summarized in a review by Subczynski et al (2012), has enabled identification of a substantial number of cholesterol functions specific to the fiber cell plasma membrane. The CBD is of crucial importance.…”

Spin-label W-band EPR with Seven-Loop–Six-Gap Resonator: Application to Lens Membranes Derived from Eyes of a Single Donor

“…1b). Profiles characterize dynamic properties of the alkyl chain that change gradually with membrane depth [23, 25]. …”

“…Lipids were derived from eyes of different species [18–20], from donors of different age [18–22], and from different regions of the eye lens, namely the cortex and nucleus [18–20]. These studies were summarized in a review [23]. Recently, we moved our studies to intact lens membranes isolated from human [24] and porcine [19] eye lenses.…”

Morphological and histological changes in eye lens: Possible application for estimating postmortem interval

“…Contains 1000-3000 layers of fiber cells [6]. The adult lens contains two kinds of fiber cells: (i) those located in the cortex (the outermost layers of the lens), which are not yet mature and still contain organelles (including mitochondria), all of which are degraded through protease-and nuclease-regulated processes, leaving behind membrane-enclosed bags of crystallines, and (ii) those located in the nucleus (the core of the lens), which are mature and do not contain organelles [6]. Into subcellular organelle evacuation during maturation is necessary to ensure the transparency of the lens, as organelles scatter light, whereas ordered proteins (crystallins) do not.…”

“…The anterior lens surface is bathed by aqueous humor, while the posterior lens surface is in contact with the vitreous body [5]. Contains 1000-3000 layers of fiber cells [6]. The adult lens contains two kinds of fiber cells: (i) those located in the cortex (the outermost layers of the lens), which are not yet mature and still contain organelles (including mitochondria), all of which are degraded through protease-and nuclease-regulated processes, leaving behind membrane-enclosed bags of crystallines, and (ii) those located in the nucleus (the core of the lens), which are mature and do not contain organelles [6].…”