The long term goal of this project is to evaluate the role of lipid peroxidation in Age Related Macular Degeneration.
The specific aims are: 1) Detection of lipid peroxidation products (oxidized fatty acids and aldehydes), and antioxidants (vitamin E, selenium, and two carotenoids, lutein and zeaxanthin) in the retina and retinal pigment epithelium from normal healthy subjects, as a function of age. 2) Evaluation of biochemical differences between the macular region and the peripheral retina, such as fatty acid composition, lipid peroxide and antioxidant levels. 3) Determination of the above antioxidants and lipid peroxidation products in retinas, and retinal pigment epithelium from subjects diagnosed with age related macular degeneration. 4) Determination of selenium in blood from subjects known with age related macular degeneration. Oxidation of polyunsaturated fatty acids leads to formation of lipid peroxides and is thought to play a significant role in retinal degeneration. Lipid peroxidation can be enhanced in the eye during dietary antioxidant deficiency and during exposure to excessive light. This biochemical mechanism is implicated in age related macular degeneration, which is the leading cause of legal blindness in the United States. The increasing life expectancy of humans is causing a rapid growth of the elder population. Therefore, age related macular degeneration will become a more prominent health problem in future years. Levels of antioxidants vitamin E, lutein and zeaxanthin carotenoids, and selenium will be measured with high performance liquid chromatography. Lipid peroxidation products, such as oxidized fatty acids and aldehydes, in particular 4-hydroxyalkenals, will be detected with sensitive and specific negative ion chemical ionization gas chromatography-mass spectrometry methods. A collaboration has been established with the Montana Eye Bank Foundation, Missoula, Montana. This eye bank supports the state program for corneal transplant surgery. The technical director, P. Buck, will supervise preparation of samples and can provide up to 200 pairs of human eyes per year.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY008818-01A2
Application #
3266167
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1992-09-30
Project End
1995-09-29
Budget Start
1992-09-30
Budget End
1993-09-29
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Montana State University Bozeman
Department
Type
Schools of Arts and Sciences
DUNS #
City
Bozeman
State
MT
Country
United States
Zip Code
59717
Sommerburg, O; Siems, W G; van Kuijk, F J (2000) Localization of carotenoids in different eye tissues. Biofactors 11:6-Mar
Fox, N E; van Kuijk, F J (1998) Immunohistochemical localization of xanthine oxidase in human retina. Free Radic Biol Med 24:900-5
Sommerburg, O; Keunen, J E; Bird, A C et al. (1998) Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes. Br J Ophthalmol 82:907-10
Mayer, M J; van Kuijk, F J; Ward, B et al. (1998) Whole blood selenium in exudative age-related maculopathy. Acta Ophthalmol Scand 76:62-7
Zang, L Y; Sommerburg, O; van Kuijk, F J (1997) Absorbance changes of carotenoids in different solvents. Free Radic Biol Med 23:1086-9
Lewis, J W; van Kuijk, F J; Carruthers, J A et al. (1997) Metarhodopsin III formation and decay kinetics: comparison of bovine and human rhodopsin. Vision Res 37:1-8
van Kuijk, F J (1997) 4-Hydroxynonenal interaction with rhodopsin. Biochem Biophys Res Commun 230:275-9
Sommerburg, O; Zang, L Y; van Kuijk, F J (1997) Simultaneous detection of carotenoids and vitamin E in human plasma. J Chromatogr B Biomed Sci Appl 695:209-15
Zang, L Y; Kalbach, H L; Brown, B et al. (1996) Elimination of n-butylated hydroxytoluene methylation during fatty acid analysis by gas chromatography. J Chromatogr B Biomed Appl 677:209-16
Siems, W G; Hapner, S J; van Kuijk, F J (1996) 4-hydroxynonenal inhibits Na(+)-K(+)-ATPase. Free Radic Biol Med 20:215-23

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