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Dissertation
The human ocular lens: a look at plasma membrane structure and molecular organization
Doctor of Philosophy (Ph.D.), Medical College of Pennsylvania and Hahnemann University
Jul 2000
DOI:
https://doi.org/10.17918/00008482
Abstract
The ocular lens is a transparent tissue that contributes to normal visual physiology by providing a means of transmitting and focusing light onto the retina. The lens is made up almost entirely of a large number of elongated, prismatic fiber cells that are compacted into highly ordered, concentric lamellae within the lens body. Fiber cells lose all subcellular organelles during their maturation; consequently, plasma membrane becomes essentially the only organelle of the lens. The fiber cell plasma membrane of the human ocular lens contains the highest relative amount of cholesterol known for mammalian cell membranes, with cholesterol/phospholipid (C/P) mole ratios ranging from 1 to 4. It was hypothesized that cholesterol, at these unusually high C/P mole ratios, organizes into discrete clusters or domains within the fiber cell plasma membrane. It was further hypothesized that reduced cholesterol content and lipid structural alterations, shown to occur in cataracts, perturb the structural organization of cholesterol in the lens membrane. To test these hypotheses, small angle x-ray diffraction approaches were used to directly examine the structural organization of lens fiber cell plasma membranes isolated from normal and cataractous human ocular lenses. Meridional diffraction patterns obtained from normal lens membranes demonstrated the presence of immiscible cholesterol bilayer domains, having a unit cell periodicity of 34.0 Å. These domains were observed in both cortical and nuclear fiber cell plasma membranes (2.4 and 3.3 C/P, respectively) and were shown to be stable over a broad range of temperature (5-40°C) and relative humidity (31-97%) levels. Similar analyses demonstrated that cataractous lens membranes, despite significantly lower (>50%) C/P mole ratios, contained more prominent and better-resolved cholesterol domains than non-cataractous controls. This paradoxical finding was consistent with the discovery that lipid peroxidation induces cholesterol domain formation in model membranes despite lower concentrations of cholesterol (0.4-0.8 C/P). These data (1) provide the first direct evidence for the existence of discrete cholesterol domains in fiber cell plasma membranes of the human ocular lens, (2) demonstrate that cholesterol domain formation increases in cataracts, and (3) suggest that lipid peroxidation may be an important mechanism by which cholesterol domain formation is enhanced in cataractogenesis.
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Details
- Title
- The human ocular lens
- Creators
- Robert Francis Jacob
- Contributors
- R. Preston Mason (Advisor) - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Awarding Institution
- Medical College of Pennsylvania and Hahnemann University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Medical College of Pennsylvania and Hahnemann University; Philadelphia, Pennsylvania
- Number of pages
- xv, 183 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Medicine (1993-1996, 1998-2002); Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Other Identifier
- 991021888717104721