Abstract
Purpose::
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.
Methods::
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.
Results::
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.
Conclusions::
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.
Keywords: age-related macular degeneration • carotenoids/carotenoid binding proteins • lipids