title: Retinal hemodynamic effects of antioxidant supplementation in an endotoxin-induced model of oxidative stress in humans.
abstract: OBJECTIVE
  The Age-Related Eye Disease Study 1 (AREDS 1) has shown that nutritional supplementation with antioxidants and zinc modifies the natural course of AMD. It is presumed that the supplements exert their beneficial effects by ameliorating oxidative stress due to the scavenging of reactive oxygen species (ROS). We have shown in a human model that under oxidative stress induced by administration of lipopolysaccharide (LPS) the vasoconstrictor response of retinal vessels to oxygen breathing is diminished. This reduced vascular response to hyperoxia was previously shown to be normalized by the AREDS 1 supplements. In the present study, we tested the hypothesis that the response can also be restored by a different antioxidant formulation.
  
  
  METHODS
  This randomized, double-masked, placebo-controlled parallel group study included 40 healthy volunteers. On each study day, retinal red blood cell (RBC) flow and the reactivity of retinal RBC flow to hyperoxia were investigated in the absence and presence of 2 ng/kg LPS. Between the two study days, subjects received either the supplement or placebo for 14 days.
  
  
  RESULTS
  Before supplementation LPS reduced retinal arterial vasoconstriction (P < 0.001) and reactivity of retinal RBC flow (P = 0.03) in response to 100% oxygen breathing. Two weeks of supplementation did not affect baseline retinal RBC flow, but normalized the LPS-induced change in the response to hyperoxia. The arterial vasoconstrictor response during LPS and 100% oxygen breathing was 4.1 ± 1.0% after administration of placebo and 10.6 ± 0.9% after supplementation (P = 0.005). The response of RBC flow to 100% oxygen breathing during LPS was 52.2 ± 2.1% after administration of placebo and 59.5 ± 2.0% after supplementation (P = 0.033).
  
  
  CONCLUSIONS
  Our data show that the supplement used in the present study can normalize the response of retinal RBC flow to hyperoxia under LPS administration. This indicates that supplementation can prevent endothelial dysfunction induced by oxidative stress, which is assumed to play a role in the pathophysiology of AMD. (ClinicalTrials.gov number, NCT00914576.).
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Told
authors.forename: Stefan
authors.initials: S
authors.lastname: Palkovits
authors.forename: Doreen
authors.initials: D
authors.lastname: Schmidl
authors.forename: Agnes
authors.initials: A
authors.lastname: Boltz
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Gouya
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
authors.forename: Katarzyna J
authors.initials: KJ
authors.lastname: Napora
authors.forename: René M
authors.initials: RM
authors.lastname: Werkmeister
authors.forename: Alina
authors.initials: A
authors.lastname: Popa-Cherecheanu
authors.forename: Gerhard
authors.initials: G
authors.lastname: Garhöfer
authors.forename: Leopold
authors.initials: L
authors.lastname: Schmetterer
mesh_terms: D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage*; D019587:Dietary Supplements; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D018384:Oxidative Stress; D011379:Prognosis; D012160:Retina / Q000187:drug effects / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000503:physiopathology / Q000517:prevention & control*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides
keywords: healthy subjects; nutritional supplementation; oxygen; retinal blood flow regulation