The human eye is continually under photooxidative stress from ambient radiation. Numerous epidemiological studies have indicated that this stress can lead to age-related modifications and ultimately various disease states in that tissue. In the lens such damage can be expressed as a cataract, whereas in the retina it has been suggested that light plays a role in macular degeneration among other diseases. Almost nothing is known about the initial photophysical and photochemical events that lead to such damage. Although those events can last only fractions of a second (in some cases as little as picosecond) subsequent biological implications can be expressed after years or even decades. By understanding the initial photophysical and photochemical processes we can more fully understand and possibly modify their deleterious effects in the eye. The present study proposes to investigate the photophysics of the major absorbing species in the lens and the retina that have been suggested to lead to disease states. These include the yellow age related protein and e-hydroxykynurenine in the human lens and lipofuscin and melanin in the human retina. This would be accomplished by the direct detection of the excited states (singlet and triplet) and the production and reaction of various short lived intermediates (eg. hydrated electron and singlet oxygen) using both pulsed and steady state techniques. These studies would be conducted: 1) at various wavelengths to determine the action spectra for the production of each intermediate for the components listed above; 2) with the addition of various exogenous quenchers such as thiols in an attempt to diminish the consequences of those photophysical events in vivo; and 3) at various ages. The last study may lead to noninvasive diagnostic techniques to detect the age-related formation of harmful compounds in the eye. These studies would lead to a thorough understanding of the interaction of light with the constituents of the eye and lead to possible remedial action to alleviate the consequences of those events.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY008883-02
Application #
3266234
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1991-02-01
Project End
1994-01-31
Budget Start
1992-02-01
Budget End
1993-01-31
Support Year
2
Fiscal Year
1992
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
Roberts, J E; Atherton, S J; Gaillard, E R et al. (1995) Age-related changes in the human lens as monitored by detection of porphyrin excited states. Photochem Photobiol 62:339-41
Gaillard, E R; Atherton, S J; Eldred, G et al. (1995) Photophysical studies on human retinal lipofuscin. Photochem Photobiol 61:448-53
Atherton, S J; Dillon, J; Gaillard, E R (1993) A pulse radiolysis study of the reactions of 3-hydroxykynurenine and kynurenine with oxidizing and reducing radicals. Biochim Biophys Acta 1158:75-82
Stevenson, S B; Cormack, L K; Schor, C M et al. (1992) Disparity tuning in mechanisms of human stereopsis. Vision Res 32:1685-94