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K. S. Crawford, P. Gaines, S. L. Breton, H. B. Chim, K. J. Lane, M. B. Abelson; Comparative Assessment of Murine Allergic Conjunctivitis Model Variations for Efficient Pre-Clinical Screening. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1933.
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In order to efficiently screen and assess potential efficacy of novel compounds for treatment of allergic conjunctivitis, a murine short ragweed (SRW) sensitization model was modified.
Balb/C and SWR mice were used in this study. Sensitization to SRW was induced using 0.5-2 mg/mL SRW in alum gel by injection either ip, into both hind footpads, or subcutaneously into both hind hocks. Response to topical ocular SRW challenge (1 mg in 5 µl PBS) was assessed at 7, 14, 21, and 28 days after sensitization as follows: Early Phase: facewashing/itching at 5 and 10 minutes post -challenge; clinical exam (conjunctival hyperemia, chemosis, lid edema, tearing/discharge) 15 minutes post-challenge; Late Phase: Histological assessments of inflammatory cell infiltration and q-PCR analysis of cytokines 6 or 24 hours after challenge. Sensitization boosters were delivered to additional groups of animals by ip injection or topical SRW drops.
Severity of the early phase response varied according to method of sensitization. Clinical response summary scores were most severe in the footpad (11.4±1.7) and the hock (9.7±0.6) as compared to ip-injected (7.6±1.9) and non-sensitized (5.2±1.0) animals (n=8 for all groups), with lid edema being the most pronounced response to challenge. There was no statistically significant difference in the response between Balb/C and SWR strains. A more severe clinical response was induced by repeated topical SRW challenge 10-14 days after initial hock injection (clinical summary score = 20.1±1.1, n=10), enabling more significant evaluation of a response to treatment, and reducing the duration of the experiment.
This model is effective for screening experimental compounds as compared to responses with known compounds as positive controls. Modifications in the model to enhance the response while reducing experiment duration improve screening efficiency. Early phase and late phase reactions, as well as inflammatory mediators, can be accurately assessed using this or other pre-clinical allergy models (rabbit 48/80, guinea pig histamine) to help elucidate the mechanism of action of novel agents as potential anti-allergy medications.
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