Carotenoid deficiency has been implicated in age-related macular degeneration (AMD) and substantial evidence links reduced bioavailability of carotenoids to inflammatory processes. This K23 project tests the unique hypothesis that systemic chronic low-grade inflammation may play a role in some AMD by means of either (1) a direct inflammatory/oxidative insult to the Bruch's membrane-retinal pigment epithelium- photoreceptor complex, or (2) by reducing the bioavailability of the macular carotenoids, lutein and zeaxanthin to the retina, either via depletion of the systemic pool, or via depletion of the intraretinal pool. The candidate will partake in a series of mentored clinical-research development activities while conducting the following sequence of studies that are designed to begin testing this hypothesis. (1) An analysis on the existing Third National Health and Nutrition Examination Survey (NHANES-III) data set to evaluate the possible association between serum levels of C-reactive protein and AMD. (2) A cross-sectional investigation on AMD in an elderly population already participating in the ongoing Dynamics of Health, Aging, and Body Composition (Health ABC) Study. A detailed retinal exam will be performed on 200 subjects likely to have some level of AMD and 100 non-affected individuals. The intraretinal optical density of lutein and zeaxanthin will be estimated non-invasively in each subject by means of a validated method based on the principle of heterochromatic flicker photometry. Macular appearance will be documented photographically and graded with an internationally approved system. Blood samples collected during this period, as part of the Health ABC Study protocol will be analyzed for levels of markers of inflammation and carotenoids. Correlations between these measures and differences associated with presence or absence of AMD will be determined in order to test the basic tenet of the inflammation-carotenoid-AMD hypothesis. Future R01 proposals would pursue whether the actual mechanisms are direct or indirect. Career development activities include: formal studies of epidemiology and biostatistics; guided training by the mentor in complex data analyses using data sets from existing studies and in design and implementation of clinical epidemiologic studies; training in macular pigment optical density measurement methods; and training in macular photograph analysis methods and fundus photography Reading Center operations.
