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Keith J. Lane, Santa J. Ono; Comparison of Alcaftadine and Olopatadine Effects on Ocular Epithelium and Eosinophil Recruitment in a Murine Model of Allergic Conjunctivitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6417.
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Antihistamines constitute the first line of therapy for allergic conjunctivitis (AC), and are safe and effective in relieving the signs and symptoms ocular allergy. Often, seasonal and perennial allergy is described as a "two phase" condition consisting of immediate (or early) and delayed (or late) responses to allergen provocation. Recent evidence suggests that changes in conjunctival epithelium may underlie some aspects of the late phase. To examine a potential role for antihistamines in attenuating late phase AC symptoms, we compared two compounds, olopatadine and alcaftadine, for their ability to modify epithelial cell changes associated with AC at time points selected to reflect the late phase
Studies employed a modified conjunctival allergen challenge (CAC) model. Sensitized mice were challenged with topical allergen with or without drug treatments. Treatment groups were assayed for acute phase (15 minutes) and delayed phase (24 hours) responses. Groups were scored for allergy symptoms (redness, itch, tearing, and edema) and for conjunctival mast cell number. Delayed-phase groups were also examined for eosinophil number and for tight junctional protein expression.
Olopatadine and alcaftadine treated animals had similar efficacy profiles and mast cell numbers, suggesting both were effective at ameliorating symptoms of the acute phase. In contrast, alcaftadine treated animals had significantly lower conjunctival eosinophil infiltration than either controls or olopatadine treated animals. Allergen challenge caused a significant decrease in expression of the junctional protein ZO-1, and this decrease was prevented by alcaftadine but not by olopatadine.
Alcaftadine displays therapeutic properties beyond its antihistamine action. These include an ability to reduce conjunctival eosinophil recruitment, and a protective effect on epithelial tight junction protein expression. We propose that alcaftadine acts to attenuate late phase AC signs and symptoms via a stabilizing effect on conjunctival epithelial layer permeability.
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