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Comparison of effects of alcaftadine and olopatadine on conjunctival epithelium and eosinophil recruitment in a murine model of allergic conjunctivitis.

Ono SJ, Lane K - Drug Des Devel Ther (2011)

Bottom Line: Olopatadine-treated and alcaftadine-treated animals had similar efficacy profiles and mast cell numbers, suggesting both were effective at ameliorating symptoms of the acute phase.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.These include an ability to reduce conjunctival eosinophil recruitment, and a protective effect on epithelial tight junction protein expression.

View Article: PubMed Central - PubMed

Affiliation: Emory University School of Medicine and Emory Eye Center, Dobbs Ocular Immunology Laboratories, Atlanta, GA, USA.

ABSTRACT

Background: Antihistamines constitute the first line of therapy for allergic conjunctivitis, and are safe and effective in relieving the signs and symptoms of ocular allergy. Despite this, they are less effective than some other drugs in relieving delayed symptoms of allergic conjunctivitis. Recent evidence suggests that changes in the conjunctival epithelium may underlie aspects of delayed reactions. In this study we compared two antihistamines, olopatadine and alcaftadine, for their ability to modify epithelial cell changes associated with allergic conjunctivitis at time points selected to reflect late-phase reactions.

Methods: Studies employed a modified conjunctival allergen challenge 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 numbers. Delayed-phase groups were also examined for eosinophil numbers and for tight junctional protein expression.

Results: Olopatadine-treated 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.

Conclusion: 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.

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Related in: MedlinePlus

Acute-phase assessments. Measures of acute response in the modified conjunctival allergen challenge assay. A) Mean values of summated symptom scores for five treatment groups. Symptoms include tearing, lid edema, conjunctival chemosis, and conjunctival redness. All treatment groups are significantly different from untreated (NS/NC, P > 0.001). B) Mast cell counts from three consecutive conjunctival tissue sections observed under a 200× field microscope. No significant differences were observed between groups. Error bars indicate standard error in both (A and B).Abbreviations: NS/NC, no sensitization, no challenge (naïve animals); S/C, sensitized, challenged; vehicle, sensitized, challenged, drug vehicle only; olopatadine, sensitized, challenged, 0.1% topical olopatadine; alcaftadine, sensitized, challenged, 0.025% topical alcaftadine.
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f1-dddt-5-077: Acute-phase assessments. Measures of acute response in the modified conjunctival allergen challenge assay. A) Mean values of summated symptom scores for five treatment groups. Symptoms include tearing, lid edema, conjunctival chemosis, and conjunctival redness. All treatment groups are significantly different from untreated (NS/NC, P > 0.001). B) Mast cell counts from three consecutive conjunctival tissue sections observed under a 200× field microscope. No significant differences were observed between groups. Error bars indicate standard error in both (A and B).Abbreviations: NS/NC, no sensitization, no challenge (naïve animals); S/C, sensitized, challenged; vehicle, sensitized, challenged, drug vehicle only; olopatadine, sensitized, challenged, 0.1% topical olopatadine; alcaftadine, sensitized, challenged, 0.025% topical alcaftadine.

Mentions: Sensitization and challenge induced significant increases in allergic signs and symptoms, including tearing and discharge, lid edema, conjunctival chemosis, and conjunctival redness (P < 0.001, Figure 1A). Although both olopatadine and alcaftadine were numerically superior to the S/C group, neither agent was statistically superior. Mast cell counts showed no significant differences between treatment groups (Figure 1B).


Comparison of effects of alcaftadine and olopatadine on conjunctival epithelium and eosinophil recruitment in a murine model of allergic conjunctivitis.

Ono SJ, Lane K - Drug Des Devel Ther (2011)

Acute-phase assessments. Measures of acute response in the modified conjunctival allergen challenge assay. A) Mean values of summated symptom scores for five treatment groups. Symptoms include tearing, lid edema, conjunctival chemosis, and conjunctival redness. All treatment groups are significantly different from untreated (NS/NC, P > 0.001). B) Mast cell counts from three consecutive conjunctival tissue sections observed under a 200× field microscope. No significant differences were observed between groups. Error bars indicate standard error in both (A and B).Abbreviations: NS/NC, no sensitization, no challenge (naïve animals); S/C, sensitized, challenged; vehicle, sensitized, challenged, drug vehicle only; olopatadine, sensitized, challenged, 0.1% topical olopatadine; alcaftadine, sensitized, challenged, 0.025% topical alcaftadine.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3038998&req=5

f1-dddt-5-077: Acute-phase assessments. Measures of acute response in the modified conjunctival allergen challenge assay. A) Mean values of summated symptom scores for five treatment groups. Symptoms include tearing, lid edema, conjunctival chemosis, and conjunctival redness. All treatment groups are significantly different from untreated (NS/NC, P > 0.001). B) Mast cell counts from three consecutive conjunctival tissue sections observed under a 200× field microscope. No significant differences were observed between groups. Error bars indicate standard error in both (A and B).Abbreviations: NS/NC, no sensitization, no challenge (naïve animals); S/C, sensitized, challenged; vehicle, sensitized, challenged, drug vehicle only; olopatadine, sensitized, challenged, 0.1% topical olopatadine; alcaftadine, sensitized, challenged, 0.025% topical alcaftadine.
Mentions: Sensitization and challenge induced significant increases in allergic signs and symptoms, including tearing and discharge, lid edema, conjunctival chemosis, and conjunctival redness (P < 0.001, Figure 1A). Although both olopatadine and alcaftadine were numerically superior to the S/C group, neither agent was statistically superior. Mast cell counts showed no significant differences between treatment groups (Figure 1B).

Bottom Line: Olopatadine-treated and alcaftadine-treated animals had similar efficacy profiles and mast cell numbers, suggesting both were effective at ameliorating symptoms of the acute phase.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.These include an ability to reduce conjunctival eosinophil recruitment, and a protective effect on epithelial tight junction protein expression.

View Article: PubMed Central - PubMed

Affiliation: Emory University School of Medicine and Emory Eye Center, Dobbs Ocular Immunology Laboratories, Atlanta, GA, USA.

ABSTRACT

Background: Antihistamines constitute the first line of therapy for allergic conjunctivitis, and are safe and effective in relieving the signs and symptoms of ocular allergy. Despite this, they are less effective than some other drugs in relieving delayed symptoms of allergic conjunctivitis. Recent evidence suggests that changes in the conjunctival epithelium may underlie aspects of delayed reactions. In this study we compared two antihistamines, olopatadine and alcaftadine, for their ability to modify epithelial cell changes associated with allergic conjunctivitis at time points selected to reflect late-phase reactions.

Methods: Studies employed a modified conjunctival allergen challenge 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 numbers. Delayed-phase groups were also examined for eosinophil numbers and for tight junctional protein expression.

Results: Olopatadine-treated 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus