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Jonathan Edward Noonan, Jie Jin Wang, William J Best, Ryan Man, Thanh T Nguyen, Gregory J Dusting, Ecosse Luc Lamoureux; Flicker Light-Induced Retinal Vasodilation is Unaffected by Inhibition of Epoxyeicosatrienoic Acids and Prostaglandins in Humans. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4338.
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The signaling molecules responsible for retinal vasodilation during flicker light stimulation are unclear, making it difficult to understand the mechanisms underpinning reduced responses in patients with chronic diseases such as diabetes. Rodent data suggest that epoxyeicosatrienoic acids (EETs) and prostaglandins (PGs) may be important mediators but corresponding data in humans are not available. We therefore investigated the effect of drugs that inhibit the conversion of arachidonic acid to EETs and PGs on retinal vessel calibers and flicker light-induced dilations in humans.
In part 1, 12 healthy non-smokers participated in a balanced crossover study over 3 visits separated by at least 2 weeks. Oral fluconazole 400 mg and dispersible aspirin 600 mg were used to inhibit the production of EETs and PGs, respectively. Functional imaging was performed with the Dynamic Vessel Analyzer (DVA, IMEDOS, Germany) 1 h after treatments. Pre-flicker arteriole and venule calibers were recorded in measurement units (MU). Maximum relative vessel dilations during 20 s of 530-600 nm diffuse luminance flicker were calculated from the mean of 3 flicker periods, each separated by 80 s. The same vessel segments were used for repeated tests. In part 2, tests were conducted in a further 12 subjects (6 fluconazole, 6 aspirin) at 30-min intervals for 2 h to characterize drug responses over time. Within-subject differences were assessed by repeated measures analysis of variance and Dunnett-adjusted pairwise comparisons.
In part 1, mean (SD) arteriole and venule calibers on no-drug visits were 119.6 (10.6) MU and 145.7 (17.0) MU, respectively. Fluconazole reduced mean venule calibers by 3.6±2.9% only. Arteriole and venule dilations on no-drug visits were 4.38% (1.96%) and 4.62% (1.75%), respectively. Drugs had no effect on dilations (all P > 0.05). In part 2, fluconazole reduced arteriole calibers by 2.4±2.9% at 2 h and venule calibers by 2.1±1.7% at 1 h, 3.6±1.7% at 1.5 h and 3.9±1.7% at 2 h. Aspirin did not affect vessel calibers (all P > 0.05). Neither fluconazole nor aspirin affected vessel dilations (all P > 0.05).
EETs may play an important role in the regulation of retinal vascular tone and blood flow under physiological conditions. However, EETs and PGs are unlikely to be primary mediators of flicker light-induced retinal vasodilation in humans.
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