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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

Alcaftadine prevents conjunctival allergen challenge-associated changes in ZO-1 and E-cadherin in conjunctival epithelium. Confocal images were used to calculate relative expression of tight junction proteins in five groups. ZO-1 expression was significantly decreased in sensitized, antigen-challenged (S/C) tissue compared with control tissue (5A, *P ≤ 0.05). Both alcaftadine and olopatadine prevented this decrease, but only alcaftadine values were significantly different from the S/C groups (**P ≤ 0.05). Differences in fluorescence intensity in E-cadherin staining (5B) between naïve and antigen-challenged groups were not significant, but treatment did result in trend of lower expression that was reversed in both active treatment groups. The only comparison that did reach the level of significance was the increase seen in alcaftadine-treated samples compared with the S/C + vehicle group (***P ≤ 0.05).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; ZO-1, zonula occludin 1.
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f5-dddt-5-077: Alcaftadine prevents conjunctival allergen challenge-associated changes in ZO-1 and E-cadherin in conjunctival epithelium. Confocal images were used to calculate relative expression of tight junction proteins in five groups. ZO-1 expression was significantly decreased in sensitized, antigen-challenged (S/C) tissue compared with control tissue (5A, *P ≤ 0.05). Both alcaftadine and olopatadine prevented this decrease, but only alcaftadine values were significantly different from the S/C groups (**P ≤ 0.05). Differences in fluorescence intensity in E-cadherin staining (5B) between naïve and antigen-challenged groups were not significant, but treatment did result in trend of lower expression that was reversed in both active treatment groups. The only comparison that did reach the level of significance was the increase seen in alcaftadine-treated samples compared with the S/C + vehicle group (***P ≤ 0.05).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; ZO-1, zonula occludin 1.

Mentions: Expression of e-cadherin and ZO-1 was also examined with immunofluorescent staining and confocal microscopy (Figure 4). These images were used to derive a quantitative comparison of expression levels in each tissue (Figures 5A and 5B). The ZO-1 expression level was significantly decreased in the S/C group compared with the NS/NC control (P ≤ 0.05). Alcaftadine 0.25% was statistically better at preventing this loss of ZO-1 expression compared with the S/C group (P < 0.05) and was not statistically different from the NS/NC control. Treatment with olopatadine 01% did not prevent ZO-1 expression loss. There was no significant difference in E-cadherin expression levels between the NS/NC and S/C groups, but a mean decrease was seen in the S/C group (Figure 5B). Alcaftadine 0.25% was statistically superior at preventing loss of E-cadherin expression compared with the S/C group (P < 0.05). Treatment with olopatadine 0.1% did not result in a statistically significant change from the S/C control. E-cadherin expression increased in both active treatment arms.


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)

Alcaftadine prevents conjunctival allergen challenge-associated changes in ZO-1 and E-cadherin in conjunctival epithelium. Confocal images were used to calculate relative expression of tight junction proteins in five groups. ZO-1 expression was significantly decreased in sensitized, antigen-challenged (S/C) tissue compared with control tissue (5A, *P ≤ 0.05). Both alcaftadine and olopatadine prevented this decrease, but only alcaftadine values were significantly different from the S/C groups (**P ≤ 0.05). Differences in fluorescence intensity in E-cadherin staining (5B) between naïve and antigen-challenged groups were not significant, but treatment did result in trend of lower expression that was reversed in both active treatment groups. The only comparison that did reach the level of significance was the increase seen in alcaftadine-treated samples compared with the S/C + vehicle group (***P ≤ 0.05).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; ZO-1, zonula occludin 1.
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Related In: Results  -  Collection

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f5-dddt-5-077: Alcaftadine prevents conjunctival allergen challenge-associated changes in ZO-1 and E-cadherin in conjunctival epithelium. Confocal images were used to calculate relative expression of tight junction proteins in five groups. ZO-1 expression was significantly decreased in sensitized, antigen-challenged (S/C) tissue compared with control tissue (5A, *P ≤ 0.05). Both alcaftadine and olopatadine prevented this decrease, but only alcaftadine values were significantly different from the S/C groups (**P ≤ 0.05). Differences in fluorescence intensity in E-cadherin staining (5B) between naïve and antigen-challenged groups were not significant, but treatment did result in trend of lower expression that was reversed in both active treatment groups. The only comparison that did reach the level of significance was the increase seen in alcaftadine-treated samples compared with the S/C + vehicle group (***P ≤ 0.05).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; ZO-1, zonula occludin 1.
Mentions: Expression of e-cadherin and ZO-1 was also examined with immunofluorescent staining and confocal microscopy (Figure 4). These images were used to derive a quantitative comparison of expression levels in each tissue (Figures 5A and 5B). The ZO-1 expression level was significantly decreased in the S/C group compared with the NS/NC control (P ≤ 0.05). Alcaftadine 0.25% was statistically better at preventing this loss of ZO-1 expression compared with the S/C group (P < 0.05) and was not statistically different from the NS/NC control. Treatment with olopatadine 01% did not prevent ZO-1 expression loss. There was no significant difference in E-cadherin expression levels between the NS/NC and S/C groups, but a mean decrease was seen in the S/C group (Figure 5B). Alcaftadine 0.25% was statistically superior at preventing loss of E-cadherin expression compared with the S/C group (P < 0.05). Treatment with olopatadine 0.1% did not result in a statistically significant change from the S/C control. E-cadherin expression increased in both active treatment arms.

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