Cholesterol Content of Focal Opacities and Multilamellar Bodies in the Human Lens: Filipin Cytochemistry and Freeze Fracture

VanMarle, Jan; Vrensen, Gijs F.J.M.

doi:10.1159/000055627

Cited by 13 publications

(5 citation statements)

References 12 publications

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“…These values were calculated for the total lipid extracts, thus including lipids from plasma membranes and lipids presented in the cytoplasm. There is evidence that multilamellar bodies presented in the cytoplasm of human aged and cataractous lenses (with a core of crystallin cytoplasm covered by multiple lipid bilayers) 50–53 contain Chol, 54,55 which may affect the Chol/PL molar ratio in plasma membranes calculated based on the total lipid extraction. These effects should be especially pronounced in fiber cells from donors with nuclear cataracts.…”

Section: Methodsmentioning

confidence: 99%

Changes in the Properties and Organization of Human Lens Lipid Membranes Occurring with Age

Mainali

Raguž

O’Brien

et al. 2016

Current Eye Research

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Purpose This research was undertaken to document the changes in the organization and properties of human lens lipid membranes that occur with age. Materials and Methods Human lens lipid membranes prepared from the total lipids extracted from clear lens cortices and nuclei of donors from age groups 0–20 and 21–40 years were investigated. An electron paramagnetic resonance technique and nitroxide spin labels (analogues of phospholipids and cholesterol) were used. Results Two distinct lipid domains, the phospholipid-cholesterol domain (PCD) and the pure cholesterol bilayer domain (CBD), were detected in all investigated membranes. Profiles of the acyl chain order, fluidity, hydrophobicity, and oxygen transport parameter across discriminated coexisting lipid domains were assessed. Independent of the age-related changes in phospholipid composition, the physical properties of the PCD remained the same for all age groups and were practically identical for cortical and nuclear membranes. However, the properties of pure CBDs changed significantly with the age of the donor and were related to the size of the CBD, which increased with the age of the donor and was greater in nuclear than in cortical membranes. A more-detailed analysis revealed that the size of the CBD was determined mainly by the cholesterol content in the membrane. Conclusions This paper presents data from four age groups: 0–20, 21–40, 41–60, and 61–70 years. Data from age groups 41–60 and 61–70 years were published previously. Combining the previously published data with those data obtained in the present work allowed us to show the changes in the organization of cortical and nuclear lens lipid membranes as functions of age and cholesterol. It seems that the balance between age-related changes in membrane phospholipid composition and cholesterol content plays an integral role in the regulation of cholesterol-dependent processes in fiber cell membranes and in the maintenance of fiber cell membrane homeostasis.

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Section: Methodsmentioning

confidence: 99%

Changes in the Properties and Organization of Human Lens Lipid Membranes Occurring with Age

Mainali

Raguž

O’Brien

et al. 2016

Current Eye Research

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“…A value of 3.0 was reported for membranes prepared from whole lens [25]. However, there is evidence that multilamellar bodies of the fiber cell cytoplasm contain Chol [37, 38] what can affect (increase) the Chol/PL molar ratio in membranes calculated based on the total lipid extraction. The relative abundance of phospholipid classes (PC, phosphatidylcholine; SM, sphingomyelin plus dihydrosphingomyelin; PS, phosphatidylserine; PE, phosphatidylethanolamine) is close to the amount reported in [22].…”

Section: Methodsmentioning

confidence: 99%

Properties of membranes derived from the total lipids extracted from the human lens cortex and nucleus

Mainali

Raguž

O’Brien

et al. 2013

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Human lens lipid membranes prepared using a rapid solvent exchange method from the total lipids extracted from the clear lens cortex and nucleus of 41- to 60-year-old donors were investigated using electron paramagnetic resonance spin-labeling. Profiles of the phospholipid alkyl-chain order, fluidity, oxygen transport parameter, and hydrophobicity were assessed across coexisting membrane domains. Membranes prepared from the lens cortex and nucleus were found to contain two distinct lipid environments, the bulk phospholipid-cholesterol domain and the cholesterol bilayer domain (CBD). The alkyl chains of phospholipids were strongly ordered at all depths, indicating that the amplitude of the wobbling motion of alkyl chains was small. However, profiles of the membrane fluidity, which explicitly contain time (expressed as the spin-lattice relaxation rate) and depend on the rotational motion of spin labels, show relatively high fluidity of alkyl chains close to the membrane center. Profiles of the oxygen transport parameter and hydrophobicity have a rectangular shape and also indicate a high fluidity and hydrophobicity of the membrane center. The amount of CBD was greater in nuclear membranes than in cortical membranes. The presence of the CBD in lens lipid membranes, which at 37°C showed a permeability coefficient for oxygen about 60% smaller than across a water layer of the same thickness, would be expected to raise the barrier for oxygen transport across the fiber cell membrane. Properties of human membranes are compared with those obtained for membranes made of lipids extracted from cortex and nucleus of porcine and bovine eye lenses.

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“…During cataractogenesis, formation of high molecular mass (HMM) aggregates cause fluctuations in protein density, resulting in light scattering and a concomitant decrease in transparency. Other factors such as multilamellar bodies and morphological changes could also contribute substantially to lens opacity [15][16][17][18] and not compaction [19]. The organellefree cytoplasm of the lens nuclear fiber cell is one such component that contains vital information about the packing and organization of crystallins critical to lens transparency.…”

Section: Cataract Disorder and Some Physico-chemical Propertiesmentioning

confidence: 99%

“…The extent of forward scattering and its influence on macular visual acuity could be important components of ophthalmological evaluations of cataract patients [16]. Filipin cytochemistry in combination with freeze fracture revealed that the amount of cholesterol in the normal fibre membranes was fully comparable with the amount of cholesterol in the deviating membranes of the focal opacities and the multilamellar bodies [17]. Increased lipid hydrocarbon chain order, variations in the headgroup and interfacial region of bilayers resulting from lipid compositional changes can influence membrane light scattering properties [18].…”

Section: Cataract Disorder and Some Physico-chemical Propertiesmentioning

confidence: 99%

Structural and Functional Properties, Chaperone Activity and Posttranslational Modifications of Alpha-Crystallin and its Related Subunits in the Crystalline Lens: N-acetylcarnosine, Carnosine and Carcinine act as Alpha- Crystallin/Small Heat Shock Protein Enhancers in Prevention and Dissolution of Cataract in Ocular Drug Delivery Formulations of Novel Therapeutic Agents

Babizhayev¹

2012

DDF

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Cataract is a leading cause of blindness worldwide and is responsible for ∼40-80% of the estimated 45 million cases of blindness that occur across the globe. In addition to providing refractive properties to the lens for focusing the image, it is believed that the molecular chaperone function of α-crystallin is essential in preventing the light scattering due to aggregation of other proteins and thus in the maintenance of lens transparency and thereby prevention of cataract. By now, it is fairly acknowledged that chaperoning ability of α-crystallin is instrumental in the maintenance of crystalline lens transparency, and decreased chaperone-like activity of α-crystallin is associated with various types and stages of cataract. A better pharmacological targeting of safeguarding the α-crystallin chaperone activity may aid the development of therapeutic strategies that could evade the need for cataract surgery and revive lens transparency of the cataractous lenses. This article originally summarizes the significance of modulation and enhancing of α-crystallin chaperone activity with imidazole-containing dipeptides N-acetylcarnosine, carnosine and carcinine in consequence to prevent, delay or dissolve the human cataract. A growing evidence and discussion of recent patents are presented in this study that demonstrate the ability of N-acetylcarnosine (lubricant eye drops) or carcinine (lubricant eye drops) (universal antioxidant and deglycation agent) resistant to enzymatic hydrolysis with carnosinase to act as pharmacological chaperones, to decrease oxidative stress and ameliorate oxidative and excessive glycation stress-related eye disease phenotypes, suggesting that the field of chaperone therapy might hold novel treatments for age-related cataracts, age-related macular degeneration (AMD) and ocular complications of diabetes (OCD). The therapeutic strategies are highlighted in the study for identifying potential chaperone compounds and for experimentally demonstrating chaperone activity in in vitro and in vivo models of human age-related eye disease, such as cataracts and advanced glycation tissue proteins - engineered systems.

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Cholesterol Content of Focal Opacities and Multilamellar Bodies in the Human Lens: Filipin Cytochemistry and Freeze Fracture

Cited by 13 publications

References 12 publications

Changes in the Properties and Organization of Human Lens Lipid Membranes Occurring with Age

Changes in the Properties and Organization of Human Lens Lipid Membranes Occurring with Age

Properties of membranes derived from the total lipids extracted from the human lens cortex and nucleus

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