Allergic conjunctivitis (AC) causes eyelid swelling, redness, tearing and itching when mast cells release mediators such as histamine (His). We reported 5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid (5,6-DiHETE), metabolite of eicosapentaenoic acid, suppressed His-induced inflammation. We investigated the therapeutic effect of 5,6-DiHETE on AC.
Mice were injected i.p. with ragweed pollen (RW) on day 0 and 5 and by eye drop on day 10-14 to induce AC. On day 14, symptoms were scored based on swelling, redness and tearing. In AC, symptom score and tear volume increased 30 minutes after RW. Histological analysis revealed mast cell degranulation and eosinophil infiltration. 300 μg/kg 5,6-DiHETE i.p. just before RW suppressed the increase in symptom score, tearing and histological change. 1 μg 5,6-DiHETE by eye drop also suppressed these symptoms.
To reveal the mechanism, we evaluated the effect on mast cell degranulation in vitro. 1 μM 5,6-DiHETE 15 minutes before antigen treatment suppressed degranulation. We further evaluated the effect on vascular hyperpermeability. 300 μg/kg 5,6-DiHETE i.p. suppressed His-induced tearing and leakage of i.v. injected dye. Orally 600 μg/kg 5,6-DiHETE also suppressed tearing.
In conclusion, 5,6-DiHETE inhibited mast cell degranulation, vascular hyperpermeability and suppressed murine AC.