The overall objective of our proposed investigation is to use state-of-the-art spectroscopic techniques to examine regional conformational; compositional and structural characteristics of lens membrane lipids and proteins. Spectroscopic findings could be related to membrane composition and performance. We will investigate normal bovine and human lenses, cataractous human lenses and lenses subjected to a variety of physicochemical stresses. Such studies well permit us to develop an in depth appreciation of relatively subtle changes in membrane properties which can lead to considerable changes in membrane performance contributing to cataractogenesis. The results of this study will strengthen the foundation of knowledge necessary to assure future development of medical therapy of human cataract.
The specific aims of this study are as follows: 1. Measure primary infrared and Raman spectroscopic characteristics of lipid vesicle dispersions obtained from normal bovine and human lenses. Spectroscopic characteristics will include: a) fluidity and phase transition temperatures; b) orthorhombic or monoclinic packing order; c) lipid head group interactions; d) lipid acyl-interface region order and packing; e) quantitate lipid saturation; f) confirm lipid composition. The membrane lipid composition of the vesicle dispersions will be determine by thin layer chromatography and high performance liquid chromatography. 2. Determine the influence of intrinsic and extrinsic membrane proteins upon spectroscopic characteristics of lens cell membranes. 3. Explore changes in spectroscopic characteristics accompanying aging of the lens and in human cataract. 4. Determine the impact of oxidative stress, UV light exposure, calcium and the cholesterol binding antibiotic filipin upon the spectroscopic characteristics of lens cell membranes and membrane lipids. 5. Explore the correlation of membrane lipid spectroscopic characteristics with lens membrane performance i.e. ATPase activity and membrane vesicle solute flux.
| Grami, Vahid; Marrero, Yernan; Huang, Li et al. (2005) alpha-Crystallin binding in vitro to lipids from clear human lenses. Exp Eye Res 81:138-46 |
| Huang, Li; Grami, Vahid; Marrero, Yernan et al. (2005) Human lens phospholipid changes with age and cataract. Invest Ophthalmol Vis Sci 46:1682-9 |
| Cenedella, Richard J; Jacob, Robert; Borchman, Douglas et al. (2004) Direct perturbation of lens membrane structure may contribute to cataracts caused by U18666A, an oxidosqualene cyclase inhibitor. J Lipid Res 45:1232-41 |
| Borchman, Douglas; Yappert, Marta C; Afzal, Muhammad (2004) Lens lipids and maximum lifespan. Exp Eye Res 79:761-8 |
| Tang, Daxin; Borchman, Douglas; Yappert, Marta C et al. (2003) Influence of age, diabetes, and cataract on calcium, lipid-calcium, and protein-calcium relationships in human lenses. Invest Ophthalmol Vis Sci 44:2059-66 |
| Tang, Daxin; Borchman, Douglas; Schwarz, Arne K et al. (2003) Light scattering of human lens vesicles in vitro. Exp Eye Res 76:605-12 |
| Byrdwell, William C; Sato, Hidetoshi; Schwarz, Arne K et al. (2002) 31P NMR quantification and monophasic solvent purification of human and bovine lens phospholipids. Lipids 37:1087-92 |
| Borchman, Douglas; Sinha, Santosh (2002) Determination of products of lipid oxidation by infrared spectroscopy. Methods Mol Biol 186:21-8 |
| Borchman, D; Giblin, F J; Leverenz, V R et al. (2000) Impact of aging and hyperbaric oxygen in vivo on guinea pig lens lipids and nuclear light scatter. Invest Ophthalmol Vis Sci 41:3061-73 |
| Zhang, Z; Zeng, J; Yin, H et al. (1999) Membrane lipid alpha-crystallin interaction and membrane Ca2+ -ATPase activities. Curr Eye Res 18:56-61 |
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