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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

Quantitation of eosinophil infiltration. Sections stained with Giemsa and hematoxylin and eosin to allow for direct counting of eosinophils; counts are from three consecutive conjunctival tissue sections. The S/C, vehicle, and olopatadine treatment groups are all significantly different from NS/NC (* P < 0.01). The alcaftadine group is not significantly different from NS/NC. Olopatadine is not significantly different from S/C or from vehicle, but alcaftadine is significantly different from both of these treatments (‡P < 0.01). The alcaftadine group is also significantly different from the olopatadine 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.
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f3-dddt-5-077: Quantitation of eosinophil infiltration. Sections stained with Giemsa and hematoxylin and eosin to allow for direct counting of eosinophils; counts are from three consecutive conjunctival tissue sections. The S/C, vehicle, and olopatadine treatment groups are all significantly different from NS/NC (* P < 0.01). The alcaftadine group is not significantly different from NS/NC. Olopatadine is not significantly different from S/C or from vehicle, but alcaftadine is significantly different from both of these treatments (‡P < 0.01). The alcaftadine group is also significantly different from the olopatadine 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.

Mentions: Changes in conjunctival eosinophil number were examined by two methods. Tissue sections from each of the five treatment groups were stained for major basic protein, a specific eosinophil cell marker. Figure 2 shows the level of eosinophil staining is dramatically increased in both S/C (Figure 2B) and vehicle (Figure 2C) conjunctiva. This increase is reduced in animals receiving olopatadine (Figure 2D) or alcaftadine (Figure 2E). Tissue sections were also stained for eosinophil cell counting; data from these experiments are shown in Figure 3. Sensitization and challenge induced a significant increase in eosinophils in the conjunctiva compared with the NS/NC group (P < 0.001). Treatment with alcaftadine 0.25% significantly inhibited eosinophil recruitment to the conjunctiva (P < 0.001) while treatment with olopatadine 0.1% did not. A direct statistical comparison between olopatadine 0.1% and alcaftadine 0.25% treatment groups found that alcaftadine 0.25% was statistically superior to olopatadine 0.1% for prevention of eosinophil recruitment (P < 0.05). Alcaftadine 0.25% was also statistically superior to vehicle-treated eyes for prevention of eosinophil recruitment to the conjunctiva (P < 0.001).


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)

Quantitation of eosinophil infiltration. Sections stained with Giemsa and hematoxylin and eosin to allow for direct counting of eosinophils; counts are from three consecutive conjunctival tissue sections. The S/C, vehicle, and olopatadine treatment groups are all significantly different from NS/NC (* P < 0.01). The alcaftadine group is not significantly different from NS/NC. Olopatadine is not significantly different from S/C or from vehicle, but alcaftadine is significantly different from both of these treatments (‡P < 0.01). The alcaftadine group is also significantly different from the olopatadine 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.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3038998&req=5

f3-dddt-5-077: Quantitation of eosinophil infiltration. Sections stained with Giemsa and hematoxylin and eosin to allow for direct counting of eosinophils; counts are from three consecutive conjunctival tissue sections. The S/C, vehicle, and olopatadine treatment groups are all significantly different from NS/NC (* P < 0.01). The alcaftadine group is not significantly different from NS/NC. Olopatadine is not significantly different from S/C or from vehicle, but alcaftadine is significantly different from both of these treatments (‡P < 0.01). The alcaftadine group is also significantly different from the olopatadine 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.
Mentions: Changes in conjunctival eosinophil number were examined by two methods. Tissue sections from each of the five treatment groups were stained for major basic protein, a specific eosinophil cell marker. Figure 2 shows the level of eosinophil staining is dramatically increased in both S/C (Figure 2B) and vehicle (Figure 2C) conjunctiva. This increase is reduced in animals receiving olopatadine (Figure 2D) or alcaftadine (Figure 2E). Tissue sections were also stained for eosinophil cell counting; data from these experiments are shown in Figure 3. Sensitization and challenge induced a significant increase in eosinophils in the conjunctiva compared with the NS/NC group (P < 0.001). Treatment with alcaftadine 0.25% significantly inhibited eosinophil recruitment to the conjunctiva (P < 0.001) while treatment with olopatadine 0.1% did not. A direct statistical comparison between olopatadine 0.1% and alcaftadine 0.25% treatment groups found that alcaftadine 0.25% was statistically superior to olopatadine 0.1% for prevention of eosinophil recruitment (P < 0.05). Alcaftadine 0.25% was also statistically superior to vehicle-treated eyes for prevention of eosinophil recruitment to the conjunctiva (P < 0.001).

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