MilliporeSigma

Serum levels of lipid metabolites in age-related macular degeneration.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2015-07-19)
Tivadar Orban, William M Johnson, Zhiqian Dong, Tadao Maeda, Akiko Maeda, Tsutomu Sakai, Hiroshi Tsuneoka, John J Mieyal, Krzysztof Palczewski
ABSTRACT

Age-related macular degeneration (AMD) is a neurodegenerative disease that causes adult-onset blindness. There are 2 forms of this progressive disease: wet and dry. Currently there is no cure for AMD, but several treatment options have started to emerge making early detection critical for therapeutic success. Analysis of the eyes of Abca4(-/-)Rdh8(-/-) mice that display light-induced retinal degeneration indicates that 11-cis-retinal and docosahexaenoic acid (DHA) levels were significantly decreased as compared with the eyes of control dark-adapted C57BL/6J mice. In addition, exposure to intense light correlated with higher levels of prostaglandin G2 in the eyes of Abca4(-/-)Rdh8(-/-) mice. Intense light exposure also lowered DHA levels in the eyes of wild-type C57BL/6J mice without discernible retinal degeneration. Analysis of human serum from patients with AMD recapitulated these dysregulated DHA levels and revealed dysregulation of arachidonic acid (AA) levels as well (∼32% increase in patients with AMD compared with average levels in healthy individuals). From these observations, we then built a statistical model that included levels of DHA and AA from human serum. This model had a 74% probability of correctly identifying patients with AMD from controls. Addition of a genetic analysis for one of the most prevalent amino acid substitutions in the age-related maculopathy susceptibility 2 gene linked to AMD, Ala(69)→Ser, did not improve the statistical model. Thus, we have characterized a reliable method with the potential to detect AMD without a genetic component, paving the way for a larger-scale clinical evaluation. Our studies on mouse models along with the analysis of human serum suggest that our small molecule-based model may serve as an effective tool to estimate the risk of developing AMD.

MATERIALS
Product Number
Brand
Product Description

SAFC
MOPS
Sigma-Aldrich
Trichloroacetic acid, ≥99.0% (titration)
Sigma-Aldrich
Trichloroacetic acid, BioXtra, ≥99.0%
Sigma-Aldrich
MOPS, ≥99.5% (titration)
Sigma-Aldrich
MOPS, BioXtra, ≥99.5% (titration)
Sigma-Aldrich
MOPS, BioPerformance Certified, suitable for cell culture, ≥99.5% (titration)
Sigma-Aldrich
Trichloroacetic acid, suitable for electrophoresis, suitable for fixing solution (for IEF and PAGE gels), ≥99%
Sigma-Aldrich
Trichloroacetic acid, ACS reagent, ≥99.0%
Sigma-Aldrich
Trichloroacetic acid, BioUltra, ≥99.5% (T)
Sigma-Aldrich
Trichloroacetic acid, ACS reagent, for the determination of Fe in blood according to Heilmeyer, ≥99.5%
Sigma-Aldrich
MOPS, anhydrous, free-flowing, Redi-Dri, ≥99.5%
Sigma-Aldrich
(R)-(−)-Phenylephrine hydrochloride, analytical standard
Sigma-Aldrich
(R)-(−)-Phenylephrine hydrochloride, powder
Sigma-Aldrich
Formic acid, ≥95%, FCC, FG
Sigma-Aldrich
(L)-Dehydroascorbic acid
Sigma-Aldrich
Deuterium, 99.8 atom % D
Sigma-Aldrich
Deuterium, 99.96 atom % D
Sigma-Aldrich
Arachidonic acid, >95.0% (GC)
Sigma-Aldrich
Dehydro-L-(+)-ascorbic acid dimer, ≥80% (enzymatic)
Sigma-Aldrich
Formic acid, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥98%
Sigma-Aldrich
Formic acid, ACS reagent, ≥96%
Sigma-Aldrich
Formic acid, reagent grade, ≥95%
Sigma-Aldrich
Formic acid, puriss., meets analytical specifications of DAC, FCC, 98.0-100%
Sigma-Aldrich
Formic acid, ACS reagent, ≥88%
Sigma-Aldrich
Arachidonic acid, from non-animal source, ≥98.5% (GC)
Sigma-Aldrich
Deuterium, 99.9 atom % D
Sigma-Aldrich
Trichloroacetic acid solution, 6.1 N
Sigma-Aldrich
cis-4,7,10,13,16,19-Docosahexaenoic acid-21,21,22,22,22-d5, ≥98 atom % D, ≥98% (CP)
Sigma-Aldrich
Deuterium hydride, extent of labeling: 96 mol% DH, 98 atom % D