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Evaluation Of EV131, A Histamine Binding Protein, In A Murine Model Of Allergic Conjunctivitis

¹ Ophthalmic Research Associates Inc North Andover MA
² Institute of Ophthalmology University College London London United Kingdom
³ Evolutec Oxford United Kingdom
⁴ Centre for Ecology and Hydrology Natural Environment Research Council Oxford United Kingdom
⁵ Schepens Eye Research Institute at Harvard Medical School Boston MA

Commercial Relationships:   M. Chapin, Optilab F; L. Nichols, Optilab F; S. Ono, None; T. Nakamura, None; W. Weston-Davies, Evolutec E; Optilab, Ltd E; G. Paesen, Evolutec P; P. Nuttall, Evolutec P; M.B. Abelson, Optilab F.

Abstract

Purpose: Ticks secrete in their saliva a family of binding proteins with anti-inflammatory activity, to counter the host's immunological response at the feeding site. EV131 is one of these proteins that binds to histamine and has mast-cells stabilizing activity. The therapeutic potential of EV131 was evaluated in a murine model of allergic conjunctivitis.
Methods: SWR/J mice were immunized with short ragweed pollen. Two weeks later, allergic conjunctivitis was induced by bilateral topical instillation of ragweed onto the eye. Clinical scores of squinting, face washing, tearing, discharge, chemosis, conjunctival redness, lid edema, and lid redness were graded on a 0-2 scale by a masked observer 15 minutes following challenge. Control animals were not sensitized but did receive topical ragweed. Mice were divided into one of three experiments. Group one was for onset of action dosed with either 1.2 EV131 (N=15 mice: 5 control mice), 2.4 mg/ml EV131 (N=8: 5 control), placebo (N=18: 8 control), or olopatadine (N=5). Drug was dosed twice daily for three days, and 15 minutes prior to challenge. Group two was to test 18 hour duration of action of 2.4 mg/ml EV131 (N=5) versus olopatadine (N=5). Drug was dosed twice daily for three days, and then 18 hours prior to challenge. Group three was to test efficacy of 2.4 mg/ml EV131 (N=6) versus olopatadine (N=6) following challenge 15 minutes after a single dose of treatment.
Results: 1.2 mg/ml EV131, 2.4 mg/ml EV131, and olopatadine reduced signs compared with placebo in all experiments. 2.4 mg/ml EV131 was superior to 1.2 mg/ml and was superior to olopatadine in reducing redness and chemosis in the duration of action test. In the single dose test, EV131 was statistically superior to olopatadine for all signs except lid edema.
Conclusion: EV131 is a potential new agent for treating allergic conjunctivitis with quick onset of action and duration of at least 18 hours in the mouse model, and is superior to the current standard olopatadine.

Keywords: 366 conjunctivitis • 437 inflammation • 435 immunomodulation/immunoregulation

© 2002, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any part of this abstract, contact the ARVO Office at arvo{at}arvo.org.