Comparative efficacy of topical antihistamines in an animal model of early phase allergic conjunctivitis

Montero, Javier A.; Ruiz-Moreno, José M.; Rodrı́guez, Alejandra; Pastor, Silvia

doi:10.1016/j.exer.2008.02.007

Cited by 15 publications

(7 citation statements)

References 29 publications

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“…Although all of these are classified as dual-action antihistamines, each has some unique spectrum of activities. For example, in vitro studies on epinastine have shown that it inhibits human mast cell secretion and synthesis of cytokines interleukin (IL)-5, IL-8, and IL-10 [35]; in contrast, ketotifen has less direct effect on these mediators but a greater mast cell-stabilizing action [36]. Subtle distinctions between each of these drugs are likely to be reflected in differences in individual clinical outcomes.…”

Section: Dual-acting Antihistamine/mast Cell-stabilizing Moleculesmentioning

confidence: 97%

Antihistamines in Ocular Allergy: Are They All Created Equal?

Abelson

McLaughlin

Gomes

2011

Curr Allergy Asthma Rep

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Use of topical antihistamines in the treatment of allergic conjunctivitis has evolved over the past several decades as our knowledge of the nature of the underlying disease has progressed. Formulations for the eye typically employ H(1)-receptor antagonists with a dual action, both directly as competitors for histamine receptor occupancy and as mast cell-stabilizing agents. Many of these compounds also display activity against late-phase allergic symptoms. Of the newest available drugs, several have a prolonged duration of action allowing once-daily dosing. Future development is likely to focus on long-acting agents such as these and on drugs that can target additional histamine receptor subtypes.

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Section: Dual-acting Antihistamine/mast Cell-stabilizing Moleculesmentioning

confidence: 97%

Antihistamines in Ocular Allergy: Are They All Created Equal?

Abelson

McLaughlin

Gomes

2011

Curr Allergy Asthma Rep

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“…For example, immune cells were found to be recruited during allergic inflammation (allergic conjunctivitis) induced by the administration of egg albumin/ragweed protein and Alum adjuvant, or adoptively transferred antigen specific T cells [36,37,45,101,103]. Leukocytes can also infiltrate into ocular tissue after topical application of irritants, e.g.…”

Section: Irritant Induced Inflammationmentioning

confidence: 99%

“…This also includes the use of apolipoprotein E dimeric peptide for herpes simplex virus infection [11], 5-LO inhibitor for respiratory syncytia virus infection [83], or anti-histamines in allergic inflammation [101]. In addition, FTY720 was also used to block the ocular infiltration of CD11b+ and CD4 T cells into mouse eyes with experimental autoimmune uveoretinitis to resolve the histological and clinical evidence of the disease [95].…”

Section: Implications Of Knowledge On Leukocyte Recruitment In Ocularmentioning

confidence: 99%

Leukocyte-endothelial interactions within the ocular microcirculation in inflammation and infection

Al-Banna

Toguri

Kelly

et al. 2013

Clinical Hemorheology and Microcirculation

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Leukocyte-endothelial interactions within the microvasculature represent a hallmark of inflammation regardless of whether the inflammation results from non-infectious or infectious triggers. In this review, we highlight features of leukocyte recruitment in ocular disease and postulate mechanisms by which the infiltrating cells may lead to the progression of the ocular inflammatory response, including cytokine and chemokine production, T cell or non-T cell responses. Additionally, ex-vivo and in vivo methods used to study the general features of the immune response are discussed, with a specific focus on intravital imaging, which allows real-time non-invasive examination of leukocyte-endothelial interactions in the ocular microvasculature. At the present time there are still significant gaps in our understanding of the process of leukocyte recruitment in vivo in different microvascular beds. Further studies using non-invasive imaging approaches, such as intravital microscopy, provide an opportunity to study dynamic tissue-specific leukocyte-endothelial interactions in vivo and identify novel targets for early intervention in the inflammatory process. This knowledge is essential to the rational use of therapeutics to resolve inflammation in ocular disease.

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“…Following drug treatment on day 23, animals were transferred to a new cage and allowed to acclimate for 30 min and then received their final OVA challenge. The itch and scratch response was monitored for up to 30 min following antigen challenge (methods adapted from Sanchis-Merino et al [22]). When more than 11 clusters of scratching had occurred, a maximum score was achieved and scratch monitoring stopped.…”

Section: Methodsmentioning

confidence: 99%

DP2 (CRTh2) Antagonism Reduces Ocular Inflammation Induced by Allergen Challenge and Respiratory Syncytial Virus

Stebbins¹,

Broadhead²,

Musiyenko

et al. 2011

Int Arch Allergy Immunol

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Background: Allergic conjunctivitis is characterized by itchy, watery and swollen eyes which occur in response to exposure to seasonal or environmental allergens. The early phase reaction of allergic conjunctivitis is primarily mediated by mast cell degranulation while the late phase reaction is driven by Th2 cells and eosinophils. Prostaglandin D₂ (PGD₂), released from mast cells, is present in allergic conjunctival tears and may elicit classical allergic responses via interaction with the high-affinity DP2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells, CRTh2). Furthermore, antagonism of this receptor is well known to inhibit eosinophil chemotaxis, basophil activation and Th2 cytokine production. PGD₂, therefore, may be involved in both early and late phase reactions in response to allergen challenge. Methods: Thus, we explored whether our novel and selective DP2 antagonist AM156 would be efficacious in animal models of allergic conjunctivitis. Furthermore, as respiratory syncytial virus (RSV) has been implicated in the pathogenesis of allergic conjunctivitis, we examined the effects of DP2 antagonism in a murine model of RSV ocular infection. Results: Utilizing a guinea pig ovalbumin model and a murine ragweed model we demonstrated that AM156 reduces redness, discharge and swelling in response to allergen challenge. These effects were equal to or greater than those of current clinical treatment options for allergic conjunctivitis including topical corticosteroids and a dual-mechanism antihistamine and decongestant. AM156 significantly reduced RSV-induced ocular inflammation and IL-4 production. Conclusion: These results suggest that a topical DP2 antagonist such as AM156 may represent a novel therapeutic for allergic conjunctivitis.

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Comparative efficacy of topical antihistamines in an animal model of early phase allergic conjunctivitis

Cited by 15 publications

References 29 publications

Antihistamines in Ocular Allergy: Are They All Created Equal?

Antihistamines in Ocular Allergy: Are They All Created Equal?

Leukocyte-endothelial interactions within the ocular microcirculation in inflammation and infection

DP2 (CRTh2) Antagonism Reduces Ocular Inflammation Induced by Allergen Challenge and Respiratory Syncytial Virus

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