The overall objective of this proposal is to study the regional conformation, composition and structural characteristics of lens membrane lipids and proteins, and relate membrane composition to membrane structure and performance (i.e. permeability, cation pump activity). We will use state of the art spectroscopic techniques to characterize normal rabbit and human lens membranes and to compare them to cataractous human lens membranes and membranes subjected to a variety of physiochemical stresses. Our hypothesis is that alterations in membrane lipid composition and structure influence membrane performance. Raman and infrared spectroscopies are among the tools that will be used to pursue six aims to test our single hypothesis. Tissues: Human lenses will be studied with respect to lens-regional changes with age and cataract type. l. What is the lipid headgroup composition in the tissues above and what is the primary structure of the unknown lipid that comprises 60% of the phospholipids? 2. What is the degree of lipid oxidation in the tissues above? oxidation will be assessed by measuring: lipid -OH and -OOH, cholesterol modifications, green and blue fluorophores and saturation. 3. How do intrinsic and extrinsic proteins influence lipid-lipid and lipid-protein interactions and, are there secondary and tertiary structural differences in membrane proteins in the tissues above? 4. What is the impact of: oxidative stress, calcium and cholesterol/filipin upon the spectroscopic characteristics of lens cell membrane and membrane lipids? 5. Do secondary products of lipid oxidation alter the secondary and tertiary structure of purified bovine crystallins or human lens homogenates? 6. What is the correlation of membrane lipid composition and structure with lens membrane performance, i.e Ca-ATPase, Na, K-ATPase and MIP26 function?
| 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 |
| Borchman, Douglas; Sinha, Santosh (2002) Determination of products of lipid oxidation by infrared spectroscopy. Methods Mol Biol 186:21-8 |
| 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, 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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