The human lens is continually under photooxidative and oxidative stress. Although light and active oxygen species have been implicated in long term changes in the human lens that lead to aging and cataractogenesis, almost nothing is known about the actual mechanism(s) by which those reactions occur. In addition the mechanism(s) by which endogenous glutathione decreases photooxidative and oxidative reactions have yet to be completely defined. The experiments outlined here will provide basic information concerning those reactions. This is an especially timely question since decreases in the ozone layer would increase photochemical stress on the lens and possibly increase the incidence of cataractogenesis. The effect of light on human lens will be thoroughly investigated by first, developing an action spectrum for the constituents of the human lens. This spectrum presents the relative photochemical damage as a function of wavelength impinging on the sample. These studies will not only given the absorbing species that initiate photochemical reactions in the lens but will also determine if there is a change in that sensitivity with age. From these studies we will ascertain the wavelengths of light that must be filtered out in order to minimize damage to the human lens. The other goals of this proposal are to define the role of light and other oxidative processes in the specific molecular changes that occur in the human lens with age as well as to determine the mechanism by which they were formed. This involves the detailed investigation of the photochemistry of the main absorbing species in the human lens, the O- beta glucoside of 3-hydroxy kynurenine and the comparison of those photooxidations with the actual molecular changes that occur in the human lens with aging. The last goal is to develop methods by which those photooxidative and oxidative changes can be retarded by supplementing the lens with glutathione mimics. These studies will be performed on the molecular (amino acid) and macromolecular (protein) levels. This type of multidimensional approach has the best chance of elucidating the role of various photooxidative and oxidative processes in aging and cataractogenesis in the human lens and the development of methods to retard them.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY002283-14A3
Application #
3256648
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1977-12-01
Project End
1996-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
14
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Rousseva, Lilia A; Gaillard, Elizabeth R; Paik, David C et al. (2007) Oxindolealanine in age-related human cataracts. Exp Eye Res 85:861-8
Dillon, James; Zheng, Lei; Merriam, John C et al. (2004) Transmission of light to the aging human retina: possible implications for age related macular degeneration. Exp Eye Res 79:753-9
Ervin, L A; Dillon, J; Gaillard, E R (2001) Photochemically modified alpha-crystallin: a model system for aging in the primate lens. Photochem Photobiol 73:685-91
Dillon, J; Zheng, L; Merriam, J C et al. (2000) Transmission spectra of light to the mammalian retina. Photochem Photobiol 71:225-9
Merriam, J C; Lofgren, S; Michael, R et al. (2000) An action spectrum for UV-B radiation and the rat lens. Invest Ophthalmol Vis Sci 41:2642-7
Gaillard, E R; Zheng, L; Merriam, J C et al. (2000) Age-related changes in the absorption characteristics of the primate lens. Invest Ophthalmol Vis Sci 41:1454-9
Paik, D C; Dillon, J (2000) The Nitrite/alpha crystallin reaction: a possible mechanism in lens matrix damage. Exp Eye Res 70:73-80
Dillon, J; Zheng, L; Merriam, J C et al. (1999) The optical properties of the anterior segment of the eye: implications for cortical cataract. Exp Eye Res 68:785-95
Dillon, J; Ortwerth, B J; Chignell, C F et al. (1999) Electron paramagnetic resonance and spin trapping investigations of the photoreactivity of human lens proteins. Photochem Photobiol 69:259-64
Dillon, J; Skonieczna, M; Mandal, K et al. (1999) The photochemical attachment of the O-glucoside of 3-hydroxykynurenine to alpha-crystallin: a model for lenticular aging. Photochem Photobiol 69:248-53

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