Choroidal Blood Flow Changes During Light/Dark Transitions Are Dependent on the Dopamine System

Abstract

Purpose:: Recently, we and others have reported that a transition from light to dark is associated with a reduction in choroidal blood flow (CBF) due to unknown mechanisms. Our results during unilateral light/dark transitions indicate that this effect is at least partially mediated via an efferent neuronal mechanism. Based on the notion that retinal dopamine levels are different in the light and dark we hypothesized that the blood flow response in the choroid to a light/dark transition may be altered by administration of dopamine antagonists.

Methods:: 19 healthy male subjects were included in this randomized placebo-controlled three way cross-over trial. On three different study days the selective D1 antagonist quetiapine, the D2 antagonist sulpiride or placebo were administered orally. CBF was measured using a compact quasi-confocal laser Doppler flowmeter, during light/dark transitions. The % change in choroidal blood flow during a light/dark transition was defined as the main outcome variable in this clinical trial. This dark reactivity was compared among the three study days using a one-way ANOVA model.

Results:: Baseline CBF was comparable on all three study days. None of the drugs altered blood pressure or pulse rate. During the light/dark transition we observed a decrease in CBF, which was reversible when the light was switched on again. The dark reactivity was 11.5 +/- 4.1 % on the placebo study day. This dark reactivity was significantly altered after administration of quetiapine (7.7 +/- 3.4 %, p < 0.05), whereas sulpiride did not alter the dark reactivity (12.5 +/- 5.3 %).

Conclusions:: Recent results in the rabbit indicate that dopamine is an endogenous vasodilator in the choroid and we have previously shown that dopamine increases CBF in healthy subjects. In the present study the D1 receptor antagonist quetiapine reduced the response of CBF during light/dark transitions indicating a role of this receptor subtype in the regulation of blood flow during changes in retinal illumination.

Clinical Trial:: www.clinicaltrials.gov NCT00280501

Keywords: dopamine • choroid