Effects of antioxidants on ocular blood flow in the LPS‐induced inflammation model in humans

Abstract

Abstract Purpose We set out to investigate whether the AREDS medication is capable of normalizing retinal blood flow reactivity to systemic hyperoxia in a human lipopolysaccharide (LPS) model. Methods The present study was a randomized double masked placebo‐controlled parallel group study in 21 healthy volunteers. The infusion of LPS was used as a standardized experimental model of systemic inflammation associated with enhanced oxidative stress and widespread endothelial dysfunction in humans. Ocular hemodynamic measurements were performed before endotoxemia and 4 hours after the subjects had received an LPS bolus. At each of these time points the retinal vascular reactivity to hyperoxia was studied. After the first trial day the subjects had to take either the AREDS medication (n=14) or a placebo (n=7) for 14 days. Thereafter a second trial day was performed on which the time schedule exactly followed the first day as described above. Results As expected LPS induced retinal vasodilatation (p < 0.01) together with an increase in retinal leukocyte density, which occurred because to systemic leukocytosis. The oxygen induced decrease in retinal blood flow was reduced after infusion of LPS (p < 0.01). This effect was partially restored after intake of the AREDS medication, but not after intake of placebo (p = 0.04) between groups. Conclusion Our findings support previous data showing that LPS induces impaired endothelial function. This effect was significantly reduced by the AREDS medication. Our model may be used to study the effects of various antioxidants and the components of the AREDS medication on oxidative stress‐induced vascular dysregulation in the human retina.