IRIS PIGMENTATION AND ATROPINE MYDRIASIS

Abstract

The pigment-dependent mydriatic effect of atropine in the eye was studied. In vitro, relative to the accumulation of 3H-atropine by the nonpigmented rabbit iris, the pigmented iris accumulated high amounts of the drug. A nonpigmented tissue, stomach fundus strip, obtained from either albino or nonalbino animals, accumulated relatively low amounts of 3H-atropine. On repeated washings, the accumulated drug from the nonpigmented tissues was rapidly lost, T1/2 [half-life] of 14 min, while that accumulated by the pigmented iris was retained longer. Although in vitro aqueous humor from serum-atropinesterase positive rabbits rapidly degraded atropine, extracts from irides of the same type of rabbit gave a single peak radioactivity, with Rf identical to the authentic atropine sulfate. The accumulation of 3H-atropine by pigmented human iris or pigment epithelium was similar to that observed for the pigmented rabbit iris. pA2 [effective concentration of against to antagonist] values of atropine from nonpigmented iris and from fundus strips varied between 8.58-8.88 with slope values close to 1. The pA2 value of atropine in pigmented iris was 8.82; at higher concentrations, atropine was less effective compared to the nonpigmented iris. In the pigmented iris the lesser effectiveness of the drug at high concentration could be explained on the basis of accumulation of the drug by the pigment cell and its constituents. The free concentration of the drug in the vicinity of the muscarinic receptor will fall. The lesser concentration will give weaker muscarinic blockade in the pigmented iris. On repeated washing, the atropine blockade of the nonpigmented iris was easily washed out, while that in the pigmented iris was retained. In vivo the relative T1/2 for the duration of atropine mydraisis in rabbits were: albino atropinesterase-positive, 3.8 h nonalbino atropinesterase-positive, 12.4 h, albino atropinesterase-negative, 29.7 h, and nonalbino atropinesterase-negative .gtoreq. 96 h. Only the latter T1/2 for the duration of action of atropine mydriasis is comparable to that observed in humans, who lack the enzyme. The role of atropinesterase and of pigment in the duration of atropine mydriasis is quite clear. The small magnitude of the mydriatic effect in humans is explained by the loss of free drug to the pigment cells and their constitutents. The longer duration of mydriatic effect in the heavily pigmented eye is explained on the basis of slow release of the accumulated drug onto the muscarinic receptor.