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2.
Am J Ophthalmol ; 153(6): 1104-9.e2, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22381365

ABSTRACT

PURPOSE: To determine if short-term Age-Related Eye Disease Study (AREDS) antioxidant and zinc supplementation affects biomarkers of oxidative stress, possibly serving as a predictor of their efficacy. DESIGN: Prospective interventional case series. METHODS: Nineteen subjects, 12 with intermediate or advanced age-related macular degeneration (AMD) (AREDS categories 3 or 4) and 7 non-AMD controls, were admitted to the Vanderbilt General Clinical Research Center and placed on a controlled diet for 7 days. Antioxidant and zinc supplements were stopped 2 weeks prior to study enrollment. Dietary supplementation with 500 mg vitamin C, 400 IU vitamin E, 15 mg ß-carotene, 80 mg zinc oxide, and 2 mg cupric oxide per day was instituted on study day 2. Blood was drawn on study days 2 and 7, and plasma concentrations of cysteine (Cys), cystine (CySS), glutathione (GSH), isoprostane (IsoP), and isofuran (IsoF) were determined. RESULTS: Short-term AREDS supplementation significantly lowered mean plasma levels of CySS in participants on a regulated diet (P = .034). No significant differences were observed for Cys, GSH, IsoP, or IsoF. There were no significant differences between AMD patients and controls. CONCLUSIONS: This pilot interventional study shows that a 5-day course of antioxidant and zinc supplements can modify plasma levels of CySS, suggesting that this oxidative stress biomarker could help predict how likely an individual is to benefit from AREDS supplementation. Further, CySS may be useful for the evaluation of new AMD therapies, particularly those hypothesized to affect redox status.


Subject(s)
Antioxidants/administration & dosage , Biomarkers/blood , Cysteine/blood , Macular Degeneration/drug therapy , Oxidative Stress , Zinc Oxide/administration & dosage , Aged , Ascorbic Acid/administration & dosage , Copper/administration & dosage , Cystine/blood , Dietary Supplements , Female , Furans/blood , Glutathione/blood , Humans , Isoprostanes/blood , Macular Degeneration/blood , Male , Pilot Projects , Prospective Studies , Vitamin E/administration & dosage , beta Carotene/administration & dosage
3.
Am J Ophthalmol ; 153(3): 460-467.e1, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22035603

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, cystine (CySS), glutathione, isoprostane, and isofuran 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 with controls (P = .013). After adjustment for age, sex, and smoking, this association was not significant. In all participants, CySS levels were associated with the CFH polymorphism rs3753394 (P = .028) as well as an 8-allele CFH haplotype (P = .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.


Subject(s)
Biomarkers/blood , Macular Degeneration/genetics , Oxidative Stress , Proteins/genetics , Aged , Case-Control Studies , Chromatography, High Pressure Liquid , Complement Factor H/genetics , Cysteine/blood , Cystine/blood , Female , Furans/blood , Genetic Predisposition to Disease , Genetic Variation , Genotype , Glutathione/blood , Humans , Isoprostanes/blood , Lipid Peroxidation , Macular Degeneration/blood , Male , Polymorphism, Single Nucleotide , Prospective Studies
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