Plasma Biomarkers of Oxidative Stress and Genetic Variants in Age-Related Macular Degeneration

Abstract

Purpose To compare plasma levels of oxidative stress biomarkers in patients with age-related macular degeneration (AMD) and controls and to evaluate a potential relationship between biochemical markers of oxidative stress and AMD susceptibility genotypes. Design Prospective case-control study Methods Plasma levels of oxidative stress biomarkers were determined in 77 AMD patients and 75 controls recruited from a clinical practice. Cysteine (Cys), cystine (CySS), glutathione (GSH), isoprostane (IsoP), and isofuran (IsoF) were measured, and participants were genotyped for polymorphisms in the complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genes. Results CySS was elevated in cases compared to controls (p = 0.013). After adjustment for age, gender, and smoking, this association was not significant. In all participants, CySS levels were associated with the CFH polymorphism rs3753394 (p = 0.028) as well as an eight-allele CFH haplotype (p = 0.029) after correction for age, gender, and smoking. None of the other plasma markers was related to AMD status in our cohort. Conclusions Our investigation of the gene/environment interaction involved in AMD revealed a relationship between a plasma biomarker of oxidative stress (CySS) and CFH genotype. These data suggest a potential association between inflammatory regulators and redox status in AMD pathogenesis.

Urinary Isoprostane Levels and Age-Related Macular Degeneration

“…The increased levels of arachidonic acid in sera of AMD patients compared with controls suggest that AMD patients may have more substrate for generation of F2-isoP than controls. 40 In a clinic-based casecontrol study involving 77 AMD patients and 75 controls, Brantley et al 24 found no significant association between plasma levels F2-IsoPs and AMD. Similarly, in the Beaver Dam Eye Study, Klein et al 23 reported that plasma levels of eight isoprostanes were not associated with 15-year cumulative incidence of AMD.…”

“…Few previous studies have examined the association of isoprostanes in plasma with AMD. 23,24,40 In a case-control study evaluating the role of serum lipids in AMD, Orban et al 40 analyzed serum lipids from 21 Japanese patients affected by neovascular AMD and 24 controls. Authors found the levels of docosahexaenoic acid, arachidonic acid, and their ratios were significantly different in AMD patients than controls.…”

“…However, the association of isoprostanes with AMD is not clear. Two previous studies that examined association between isoprostanes measured using immunoassays and AMD 23,24 did not find any significant association. 25,26 In the current study, we evaluated the association of AMD with oxidative stress as indicated by urinary F2-isoprostanes (F2-IsoPs) measured by gas chromatography tandem mass spectrometry (GC-MS), the gold standard method for measuring isoprostanes 25,26 in a population-based sample of adults in Singapore…”

Lipid peroxidation generates biologically active phospholipids including oxidatively N-modified phospholipids

“…Esterified IsoF also form in the liver after carbon tetrachloride poisoning (Song et al, 2008). Plasma levels of unesterified IsoF, which likely reflect at least to some extent changes in esterified IsoF in tissue, are elevated in age-related macular degeneration, severe sepsis, mercury exposure, acute kidney injury, and preterm resuscitation (Alkazemi et al, 2013; Billings et al, 2011; Brantley et al, 2012; Montine et al, 2004; Vento et al, 2009; Ware et al, 2011). …”

Non-aqueous microchip electrophoresis for characterization of lipid biomarkers

“…Table 1 depicts the S/N ratio for lipid concentrations in the range 100 pM , C , 1 mM. Conservatively interpreting these data indicates that the LOD of the current system is approximately 1-10 pM, a range acceptable for fluorescence-based assay development and easily competent for the determination of circulating plasma biomarkers [39][40][41]. For example, millimolar lipid and protein levels and micromolar vitamin concentrations in plasma were used by Karaouzene et al [42] to determine that obesity induces both oxidative stress and lipid composition changes in men.…”