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P. Bhosale, B. Serban, P. S. Bernstein; Very-Long-Chain Fatty Acids and Macular Carotenoid Metabolites Are Biomarkers of Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2142.
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Lipophilic nutritional factors such as omega-3 fatty acids and carotenoids exert several important biological effects that may protect against retinal degenerative diseases such as age-related macular degeneration (AMD). The upcoming Age-Related Eye Disease Study II (AREDS II) is specifically focusing on the potential protective roles of the macular carotenoids and omega-3 fatty acids; however, experimental and epidemiological data to date have not clearly established the major biochemical mechanisms behind the protective effect of these molecules.
Macula, peripheral retina, and retinal pigment epithelium (RPE) samples (all 8-mm punches) from 19 donor eyes with a history of AMD and 21 age-matched normal donors were procured from the local eye bank. Carotenoid and fatty acid profiles were determined by HPLC or GC coupled with in-line single quadrupole mass spectrometers (MS), respectively.
A) Carotenoids: We observed lower levels of total macular carotenoids (18.8 ±7.2 ng, n=19) relative to age-matched normals (28.4 ±12.6 ng, n=21). 3-Methoxyzeaxanthin (3-MZ), a macula specific zeaxanthin metabolite, was higher in the AMD donor eyes (4.1 ±4.7, n=19) in comparison to age matched donors (1.9 ±1.3, n=21, p < 0.001). B) Total fatty acids: We observed similar distributions of myristic (C14), palmitic (C16), stearic (C18), oleic (C18:1 (n-6)), linoleic (C18:2 (n-6)), and arachidonic (C20:4 (n-6)) fatty acids in AMD and age-matched donor retinas. Retinas of AMD donor eyes had significantly less docosahexaenoic acid (DHA, C22:6 (n-3)) in comparison to normal donors. The RPE from AMD donors had a distinct accumulation of monounsaturated 15-tetracosenoic acid (nervonate; C24:1 (n-9)) and saturated tetracosanoic acid (lignocerate; C24) as well as some C26 and longer lipids, all of which were completely absent in age-matched normal donors.
3-Methoxyzeaxanthin and certain very-long-chain fatty acid are biomarkers for age-related ocular disorders in the macula and RPE, respectively. Understanding the underlying mechanisms for the accumulation of these biomarkers will help in elucidating the biochemical mechanisms of AMD pathology.
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