Long-term objectives: Primate retinas have a yellow macular pigment that is thought both to enhance visual resolution and to protect the retina and retinal pigment epithelium (RPE) from oxidative damage. It is likely that some people with low pigment densities are at risk for chronic retinal damage and age-related macular degeneration. Our goal is to identify nutritional and retinal factors contributing to the protection of the retina by retinal carotenoids and Vitamin E. The idea that macular pigment contributes to refined visual resolution (acuity) in the fovea will be critically tested.
Specific Aims : I. Identify factors underlying individual differences in density of macular pigmentation. Manipulate dietary levels of carotenoids while monitoring the resultant changes in the blood and the retinas of monkeys. Determine whether differences in macular pigment density are linked to differences in cone density in macaques and humans. II. Compare the spatial distributions of macular pigment carotenoids and Vitamin E. Compare the spatial distributions of the carotenoids comprising the macular pigment with the spatial distribution of Vitamin E in monkey and human retinas by microdissection and biochemical analyses. Determine whether Vitamin E is selectively associated with rod photoreceptors, which are known to be lost with aging. III. Measure the optical density profile of human macular pigment and assess its importance for visual performance. The spatial profile of human macular pigment density will be measured and compared with the spatial dimensions of the foveal depression. Noninvasive techniques will be utilized to study human macular pigment in vivo accurately and efficiently. Postmortem donor retinas will be studied in histological preparations to confirm the general features of the in vivo data. Individual differences in macular pigment density will be correlated with blood levels of macular pigment carotenoids. Subjects will include both genders and a cross section of ages and ethnic backgrounds from the local population. Visual resolution (acuity and contrast sensitivity) of subjects with high and low macular pigment will be tested to determine whether macular pigment improves visual performance. Methodology: The macular pigment carotenoids and Vitamin E will be measured in blood and retina by HPLC. In vivo measures of macular pigment in monkeys and some humans will be made by two-wavelength (photographic) reflectometry. The reflectometry data will be validated for monkeys by densitometry of retinal whole mounts, and for humans by psychophysical threshold testing. In older human subjects, much of the in vivo data will be gathered by psychophysical measurements. Retinal rod and cone distributions will be mapped by Nomarski imaging of retinal whole mounts. Health Relatedness: Older people are protected against the neovascular form of age-related macular degeneration by higher blood levels of carotenoids and other antioxidants. Thus manipulation or supplementation of the diet offers hope for preventive therapy. Our basic research project will provide essential data and techniques for deriving the maximum benefit from large, expensive clinical trials that are currently being initiated.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY004911-07A4
Application #
3259527
Study Section
Special Emphasis Panel (ZRG1-VISB (02))
Project Start
1983-09-30
Project End
1996-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Schepens Eye Research Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02114
Delori, F C; Goger, D G; Hammond, B R et al. (2001) Macular pigment density measured by autofluorescence spectrometry: comparison with reflectometry and heterochromatic flicker photometry. J Opt Soc Am A Opt Image Sci Vis 18:1212-30
Hammond Jr, B R; Wooten, B R; Snodderly, D M (1998) Preservation of visual sensitivity of older subjects: association with macular pigment density. Invest Ophthalmol Vis Sci 39:397-406
Hammond Jr, B R; Wooten, B R; Snodderly, D M (1997) Density of the human crystalline lens is related to the macular pigment carotenoids, lutein and zeaxanthin. Optom Vis Sci 74:499-504
Crabtree, D V; Snodderly, D M; Adler, A J (1997) Retinyl palmitate in macaque retina-retinal pigment epithelium-choroid: distribution and correlation with age and vitamin E. Exp Eye Res 64:455-63
Snodderly, D M; Shen, B; Land, R I et al. (1997) Dietary manipulation of plasma carotenoid concentrations of squirrel monkeys (Saimiri sciureus). J Nutr 127:122-9
Hammond Jr, B R; Wooten, B R; Snodderly, D M (1997) Individual variations in the spatial profile of human macular pigment. J Opt Soc Am A Opt Image Sci Vis 14:1187-96
Hammond Jr, B R; Johnson, E J; Russell, R M et al. (1997) Dietary modification of human macular pigment density. Invest Ophthalmol Vis Sci 38:1795-801
Crabtree, D V; Adler, A J; Snodderly, D M (1996) Radial distribution of tocopherols in rhesus monkey retina and retinal pigment epithelium-choroid. Invest Ophthalmol Vis Sci 37:61-76
Crabtree, D V; Adler, A J; Snodderly, D M (1996) Vitamin E, retinyl palmitate, and protein in rhesus monkey retina and retinal pigment epithelium-choroid. Invest Ophthalmol Vis Sci 37:47-60
Hammond Jr, B R; Fuld, K; Snodderly, D M (1996) Iris color and macular pigment optical density. Exp Eye Res 62:293-7

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