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| Paul
S. Bernstein, M.D., Ph.D.
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| Goal: To identify the genetic and environmental
factors that lead to age-related macular degeneration (AMD)
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Macular
dystrophy in a member of a large Utah family with an inherited defect in ELOVL4,
a gene involved in long-chain fatty acid metabolism in the human retina.
1) Biochemistry
and pharmacology of the macular carotenoids. The
macular carotenoids, lutein and zeaxanthin, are dietary factors derived
from fruits and vegetables that are found in extremely high concentrations
in the macula of the human retina, where they appear to play an important
protective role in the prevention of AMD through antioxidant and
light-screening mechanisms. We are purifying and characterizing the
binding proteins responsible for the specific uptake and stabilization of
lutein and zeaxanthin in the human macula, and we are defining the
pathways of carotenoid metabolism in the retina. Understanding their roles
may guide rational treatments and preventative strategies against AMD.
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2)
Resonance Raman measurement of macular carotenoids in the living human
eye. We have developed
and patented a novel, noninvasive optical method to quantify levels of the
macular carotenoids lutein and zeaxanthin in the living human eye by using
resonance Raman spectroscopy. Clinical
trials are in progress to measure macular carotenoids in normal and AMD
patients. This test may be used some day for the early identification of
individuals at risk for visual loss from AMD.
3) Genetics of
age-related macular degeneration.
The occurrence of age-related macular degeneration is mediated in
part by inherited susceptibility factors, and by environmental factors
such as smoking, light exposure, and diet.
We have already identified two genes, ABCR
and ELOVL4, that are involved in
inherited macular degenerations such as AMD, Stargardt disease, and
pattern dystrophy. Utah‘s population of large families with well defined
genealogy are an ideal resource for the identification of new genes
responsible for AMD. |
| Ongoing
Collaborations |
| F.
Khachik, University of Maryland - Carotenoid metabolism
R. Allikmets, Columbia University - AMD
genetics
J. Seddon, Harvard University - AMD
genetics
M. Leppert, University of Utah - AMD
genetics
W. Gellermann, University of Utah - Raman
spectroscopy
W. Askew, University of Utah - AMD
nutritional studies
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| Selected
Publications |
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Bernstein
PS, Yoshida MD, Katz NB, McClane RW, Gellermann W (1998).
Raman detection of macular carotenoid pigments in intact human
retina. Invest Ophthalmol Vis
Sci 39: 2003-2011.
Bernstein
PS, Gellermann W, McClane RW (1999).
Method and system for measurement of macular carotenoid
levels. US Patent #5,873,831.
Allikmets
R, and the International ABCR
Screening Consortium (2000). Further evidence for an association of ABCR
alleles with age-related macular degeneration. Am
J Human Gen 67: 487-491.
Bernstein
PS, Khachik F, Carvalho LS, Muir GJ, Zhao, D-Y, Katz NB
(2001). Identification and quantitation of carotenoids and their
metabolites in the tissues of the human eye. Exp
Eye Res 72: 215-223.
Yemelyanov
AY, Katz NB, Bernstein PS (2001). Ligand-binding
characterization of xanthophyll carotenoids to solubilized membrane
proteins derived from human retina. Exp
Eye Res72: 381-392.
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