Ocular Effects of Cysteinyl Leukotrienes
Allergic conjunctivitis (AC) is the inflammatory response to the direct exposure of the conjunctivae to an allergen
Numerous studies report elevated levels of CysLTs in various forms of AC, both acutely and in late phase, and that CysLTs play a role in the development of chronic and more severe forms of the disease. The allergic reaction occurring primarily in the nasal mucosa can induce a secondary conjunctival response of an immediate, late or delayed response in patients with AC.
Our development is focused on further validating the target in human trials for allergic eye disorders
Zafirlukast: Validated in Animal Models of Allergic Eye Disorders
One of the main mechanisms underlying the pathogenesis of allergic conjunctivitis is increased secretion of mucin by goblet cells. Both CysLT1 and CysLT2 are expressed by rat conjunctiva and in cultured rat and human conjunctival goblet cells.
Experimental studies of topical zafirlukast (instillation) in challenged eyes of Wistar rats demonstrated zafirlukast reversed the effect of C48/80 on late-phase nitric oxide component of conjunctival hypersensitivity response.
Clinical Validation of the Class of LTRAs in Treating Allergic Eye Disorders
Treatment with the LTRA-antagonist (montelukast) led to a marked reduction in the amount of mucin secreted by LTD4timulated goblet cells. Involvement of the CysLTs pathway in allergic conjunctivitis was also indicated in a clinical trial of orally administered montelukast in patients with both vernal keratoconjunctivitis and asthma; the trial reported a reduction in the severity of ocular signs and symptoms.
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An environmental challenge (“The Park Study”) showed a reduction in ocular signs and symptoms (data on file AstraZeneca) with single oral doses of zafirlukast in a dose-response manner.
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Review of clinical studies and case reports found a significant and persistent reduction of ocular signs and symptoms in asthmatic patients with vernal keratoconjunctivitis treated with oral montelukast.
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Montelukast and zafirlukast are used interchangeably in clinical practice.