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Elzbieta Polska, MD; Arno Doelemeyer, MSc; Alexandra Luksch, MD; Paulina Ehrlich, MD; Nils Kaehler, MD; Christine L. Percicot, MD; George N. Lambrou, MD; Leopold Schmetterer, PhD

Arch Ophthalmol. 2002;120:348-352.

Background  There is increasing evidence that reduced ocular blood flow plays a role in the pathogenesis of glaucoma. In patients with normal-tension glaucoma, ocular blood flow abnormalities may be associated with dysfunction of the endothelin 1 (ET-1) regulation system.

Objective  To test the hypothesis that unoprostone, a topical docosanoid, may affect ET-1–induced vasoconstriction in the human choroid.

Methods  In a placebo-controlled, randomized, double-masked, 2-way crossover design, ET-1 (2.5 ng/kg per minute for 150 minutes) was administered intravenously to 24 healthy individuals. Thirty minutes after the start of ET-1 infusion, 1 drop of unoprostone or placebo was instilled into the right eye. After another 30 minutes, 2 drops of unoprostone or placebo was topically administered. This procedure was continued and the dose was increased further until 4 drops of unoprostone or placebo was reached. Subfoveal and pulsatile choroidal blood flow were assessed using laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude, respectively.

Results  Administration of exogenous ET-1 decreased choroidal blood flow (mean ± SEM, 17% ± 2%; P<.001) and fundus pulsation amplitude (mean ± SEM, 19% ± 2%; P<.001). This effect was significantly blunted when topical unoprostone was coadministered (mean ± SEM decrease in choroidal blood flow, 7% ± 2%; P = .04 vs placebo; mean ± SEM decrease in fundus pulsation amplitude, 12% ± 2%; P<.001 vs placebo).

Conclusion  There is a functional antagonism between ET-1 and topical unoprostone in the choroidal vasculature.

Clinical Relevance  Our findings of a functional antagonism between ET-1 and topical unoprostone in the choroidal vasculature may be important in vascular eye diseases associated with increased ET-1.

From the Department of Clinical Pharmacology (Drs Polska, Luksch, Ehrlich, Kaehler, and Schmetterer and Mr Doelemeyer) and the Institute of Medical Physics (Dr Schmetterer), Vienna University, Vienna, Austria; Novartis Ophthalmics, Basel, Switzerland (Drs Percicot and Lambrou and Mr Doelemeyer); and University Eye Clinic, Strasbourg, France (Dr Lambrou).

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