The human macula, the specialized region of the retina responsible for high resolution visual acuity, selectively accumulates two xanthophy11 carotenoids derived from the diet, lutein and zeaxanthin. Several recent epidemiological studies have demonstrated a strong inverse correlation between dietary intake of lutein and zeaxanthin and the risk of progression Age-Related Macular Degeneration (AMD) the leading cause of blindness among the elderly in the United States. It is thought that the macular carotenoids protect against least-induced damage to the retina by filtering out damaging wavelengths of light and by acting as antioxidants. The biochemical mechanisms that mediate the selective uptake, concentration, and stabilization of the macular carotenoids are unknown. In lower animals, such as lobsters and cyanobacteria, specialized carotenoid-binding proteins perform these tasks. It is hypothesized that comparable carotenoid-binding proteins may have a similar role in the human macula. A major goal of this project is to understand the biochemical processes responsible for the specific deposition of lutein and zeaxanthin the macula, with special emphasis on the search for potential carotenoid-binding proteins. This project will also investigate the properties of carotenoid- protein and carotenoid-lipid interactions through quantitative binding studies and various spectroscopic methods, including resonance Raman spectroscopy, in model systems and in intact retinal tissue. The experiments of this proposal may provide new insights into the biochemical basis of the specific uptake lutein and zeaxanthin into the macula. Derangements of the mechanisms of uptake and stabilization of the macular carotenoids could have profound impact on the progression of AMD and inherited retinal dystrophies. Anticipated interventional clinical studies may be able to take advantage of the specific uptake systems to increase the level of macular carotenoid pigment and perhaps retard or prevent the progressive blindness produced by these diseases.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29EY011600-04
Application #
6179106
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Dudley, Peter A
Project Start
1997-08-01
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
4
Fiscal Year
2000
Total Cost
$104,650
Indirect Cost
Name
University of Utah
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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Shyam, Rajalekshmy; Vachali, Preejith; Gorusupudi, Aruna et al. (2017) All three human scavenger receptor class B proteins can bind and transport all three macular xanthophyll carotenoids. Arch Biochem Biophys 634:21-28
Shyam, Rajalekshmy; Gorusupudi, Aruna; Nelson, Kelly et al. (2017) RPE65 has an additional function as the lutein to meso-zeaxanthin isomerase in the vertebrate eye. Proc Natl Acad Sci U S A 114:10882-10887
Horvath, Martin P; George, Evan W; Tran, Quang T et al. (2016) Structure of the lutein-binding domain of human StARD3 at 1.74?Å resolution and model of a complex with lutein. Acta Crystallogr F Struct Biol Commun 72:609-18
Tanprasertsuk, Jirayu; Li, Binxing; Bernstein, Paul S et al. (2016) Relationship between Concentrations of Lutein and StARD3 among Pediatric and Geriatric Human Brain Tissue. PLoS One 11:e0155488

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