This application is to continue our studies of "Diet and Lifestyle Factors Reducing Risk for Age-Related Eye Disease" and addresses the National Eye Institute's priority for research to "Delineate the interacting roles of the environment and genetics as risk factors for retinal disease." Unique to these studies is the assessment of the importance of vitamin D status, carotenoid status and scores on broad healthy diet patterns. This is the largest sample, world-wide, that incorporates both eye photographs which document stages of age-related macular degeneration and measurements of the density of the carotenoids in the macula of the eye, where this condition develops. Previous funding has permitted the collection of the most comprehensive set of nutritional data available to evaluate as predictors of lower prevalence of age-related macular degeneration (AMD), an average of six-years later in women 50-79 years of age from three US states in the Carotenoids in Age- Related Eye Disease Study (N=1,787). Because eye photographs identify early changes, before most women are aware of their presence, we were able to study modifiable dietary and lifestyle habits during periods of time when they are likely to influence early stages. We recently reported evidence to support protective roles of vitamin D, the macular carotenoids, lutein and zeaxanthin, healthy diet patterns and physical activity against the development of early/intermediate stages of AMD. There is strong evidence that these early changes are highly predictive of developing advanced stages. However, these previous estimates are "averages" of the strength of associations across people who differ in genetic propensity for developing AMD. This project, which is ancillary to the Women's Health Initiative, has access to DNA from stored blood samples which we will use to characterize women for high risk genotypes which have strongly predicted risk for AMD in recent large studies and to characterize women with good status of vitamin D and retinal carotenoids. We will use these data to calculate genetic risk rank scores reflect level of overall genetic susceptibility to AMD. We will then evaluate whether the strengths of associations of healthy diets and lifestyles to AMD in people who have high, genetic risk rank scores, compared with women who have low scores. These insights about the range of importance of nutritional factors based on genetic susceptibility will help identify strategies that physicians and public health officials can use to inform people of diets that may lower risk for developing and worsening AMD, to target people who will benefit most, and to motivate people to adopt preventive strategies. The addition of genotyping for candidate genes which have recently been related to the status of carotenoids and vitamin D may also suggest new genetic predictors of AMD and provide insights about mechanisms by which lutein and zeaxanthin, and vitamin D, protect against AMD.

Public Health Relevance

We recently reported evidence to support protective roles of vitamin D, the macula carotenoids lutein and zeaxanthin, healthy diet patterns and physical activity against the development of early/intermediate stages of AMD. These studies further evaluate whether being genetically susceptible for developing AMD further enhances the protective benefit of healthy diets and healthy lifestyles. The findings can be used by physicians and public health officials to inform people of healthy habits which may lower risk for developing and worsening AMD, to target people who will benefit most, and to motivate people to adopt preventive strategies. These changes could dramatically lower health care expenditures devoted to treating age-related macular degeneration which are expected to rise as the United States population ages in the coming decades.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY016886-05
Application #
8386611
Study Section
Special Emphasis Panel (ZEY1-VSN (09))
Program Officer
Wideroff, Louise
Project Start
2005-08-01
Project End
2014-11-30
Budget Start
2012-12-01
Budget End
2014-11-30
Support Year
5
Fiscal Year
2013
Total Cost
$247,774
Indirect Cost
$80,923
Name
University of Wisconsin Madison
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Meyers, Kristin J; Mares, Julie A; Igo Jr, Robert P et al. (2014) Genetic evidence for role of carotenoids in age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS). Invest Ophthalmol Vis Sci 55:587-99
Engelman, Corinne D; Meyers, Kristin J; Iyengar, Sudha K et al. (2013) Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations. J Nutr 143:17-26
McKay, Gareth J; Loane, Edward; Nolan, John M et al. (2013) Investigation of genetic variation in scavenger receptor class B, member 1 (SCARB1) and association with serum carotenoids. Ophthalmology 120:1632-40
Meyers, Kristin J; Johnson, Elizabeth J; Bernstein, Paul S et al. (2013) Genetic determinants of macular pigments in women of the Carotenoids in Age-Related Eye Disease Study. Invest Ophthalmol Vis Sci 54:2333-45
Mares, Julie A; Voland, Rick P; Sondel, Sherie A et al. (2011) Healthy lifestyles related to subsequent prevalence of age-related macular degeneration. Arch Ophthalmol 129:470-80
Millen, Amy E; Voland, Rick; Sondel, Sherie A et al. (2011) Vitamin D status and early age-related macular degeneration in postmenopausal women. Arch Ophthalmol 129:481-9
Freedman, Laurence S; Midthune, Douglas; Carroll, Raymond J et al. (2011) Using regression calibration equations that combine self-reported intake and biomarker measures to obtain unbiased estimates and more powerful tests of dietary associations. Am J Epidemiol 174:1238-45
Kluczynski, Melissa A; Lamonte, Michael J; Mares, Julie A et al. (2011) Duration of physical activity and serum 25-hydroxyvitamin D status of postmenopausal women. Ann Epidemiol 21:440-9
Mares, Julie A; Voland, Rick; Adler, Rachel et al. (2010) Healthy diets and the subsequent prevalence of nuclear cataract in women. Arch Ophthalmol 128:738-49
Freedman, Laurence S; Tasevska, Natasa; Kipnis, Victor et al. (2010) Gains in statistical power from using a dietary biomarker in combination with self-reported intake to strengthen the analysis of a diet-disease association: an example from CAREDS. Am J Epidemiol 172:836-42