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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23EY000409-02
Application #
6518263
Study Section
Special Emphasis Panel (ZEY1-VSN (02))
Program Officer
Kurinij, Natalie
Project Start
2001-05-01
Project End
2006-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
2
Fiscal Year
2002
Total Cost
$149,783
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Iannaccone, Alessandro; Giorgianni, Francesco; New, David D et al. (2015) Circulating Autoantibodies in Age-Related Macular Degeneration Recognize Human Macular Tissue Antigens Implicated in Autophagy, Immunomodulation, and Protection from Oxidative Stress and Apoptosis. PLoS One 10:e0145323
Vishwanathan, Rohini; Iannaccone, Alessandro; Scott, Tammy M et al. (2014) Macular pigment optical density is related to cognitive function in older people. Age Ageing 43:271-5
Iannaccone, Alessandro; Neeli, Indira; Krishnamurthy, Pratheebha et al. (2012) Autoimmune biomarkers in age-related macular degeneration: a possible role player in disease development and progression. Adv Exp Med Biol 723:11-6
Sanders, Jason L; Iannaccone, Alessandro; Boudreau, Robert M et al. (2011) The association of cataract with leukocyte telomere length in older adults: defining a new marker of aging. J Gerontol A Biol Sci Med Sci 66:639-45
Spencer, Kylee L; Olson, Lana M; Schnetz-Boutaud, Nathalie et al. (2011) Using genetic variation and environmental risk factor data to identify individuals at high risk for age-related macular degeneration. PLoS One 6:e17784
Iannaccone, Alessandro; Fung, Kenneth H; Eyestone, Mari E et al. (2009) Treatment of adult-onset acute macular retinoschisis in enhanced s-cone syndrome with oral acetazolamide. Am J Ophthalmol 147:307-312.e2
Gallaher, Kevin T; Mura, Marco; Todd, Wm Andrew et al. (2007) Estimation of macular pigment optical density in the elderly: test-retest variability and effect of optical blur in pseudophakic subjects. Vision Res 47:1253-9
Iannaccone, Alessandro; Mura, Marco; Gallaher, Kevin T et al. (2007) Macular pigment optical density in the elderly: findings in a large biracial Midsouth population sample. Invest Ophthalmol Vis Sci 48:1458-65
Jablonski, Monica M; Iannaccone, Alessandro; Reynolds, Drew H et al. (2007) Age-related decline in VIP-positive parasympathetic nerve fibers in the human submacular choroid. Invest Ophthalmol Vis Sci 48:479-85