Effects of Antioxidants (AREDS Medication) on Ocular Blood Flow and Endothelial Function in an Endotoxin-Induced Model of Oxidative Stress in Humans

The Age-Related Eye Disease Study (AREDS) has shown that supplementation of antioxidants slows the progression of age-related macular degeneration (AMD). The mechanism underlying this therapeutic effect may be related to a reduction of reactive oxygen species (ROS). The authors have recently introduced a model showing that the response of retinal blood flow (RBF) to hyperoxia is diminished by administration of lipopolysaccharide (LPS). In the present study, the hypothesis was that this response can be restored by the AREDS medication. Twenty-one healthy volunteers were included in this randomized, double-masked, placebo-controlled, parallel group study. On each study day, RBF and the reactivity of RBF to hyperoxia were investigated before and after infusion of 2 ng/kg LPS. Between the two study days, subjects took either the AREDS medication or placebo for 14 days. After administration of LPS reduced retinal arterial vasoconstriction during hyperoxia (AREDS group: 12.5% +/- 4.8% pre-LPS vs. 9.4% +/- 4.6% post-LPS; placebo group: 9.2% +/- 3.3% pre-LPS vs. 7.1% +/- 3.5% post-LPS) and a reduced reactivity of RBF during hyperoxia (AREDS: 50.4% +/- 8.9% vs. 44.9% +/- 11.6%, placebo: 54.2% +/- 8.6% vs. 46.0% +/- 6.9%) was found. The reduced responses were normalized after 2 weeks of AREDS antioxidants but not after placebo (vasoconstriction: 13.1% +/- 4.5% vs. 13.1% +/- 5.0% AREDS, 11.2% +/- 4.2 vs. 7.4% +/- 4.2% placebo; RBF: 52.8% +/- 10.5% vs. 52.4% +/- 10.5% AREDS, 52.4% +/- 9.3% vs. 44.2% +/- 6.3% placebo). The sustained retinal vascular reaction to hyperoxia after LPS in the AREDS group indicates that antioxidants reduce oxidative stress-induced endothelial dysfunction, possibly by eliminating ROS. The model may be an attractive approach to studying the antioxidative capacity of dietary supplements for the treatment of AMD (ClinicalTrials.gov number, NCT00431691).