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R. P. Barrett, E. A. Berger, L. D. Hazlett; Development and Preliminary Characterization of the Marmoset Monkey as a Translational Model of P. aeruginosa Corneal Infection and Treatment. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3894.
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Ocular infection was induced in the marmoset monkey using similar techniques as performed in the mouse model. Briefly, two marmoset monkeys were anesthetized and the right eye of each animal was scarified. A 10 µL aliquot (1 × 106 CFU P. aeruginosa ATCC strain 19660) was topically applied to the wounded cornea. The experimental animal received daily i.p. injections of VIP (5 nM in 400 µL) and the control animal similarly received PBS. At 72 h post infection (p.i.), disease was graded and documented photographically and histologically. In addition, mRNA expression levels of 84 genes from VIP-treated and PBS-treated corneas were profiled by RT2 ProfilerTM PCR Array and reviewed in light of the mouse system.
Similar to the mouse model, less disease was observed and documented photographically and histologically after VIP versus PBS treatment. Genes (chosen based on previous mouse data) were found to be differentially regulated with VIP treatment compared to PBS after infection. Transcript levels of IL-1β, IL-8 (human homolog of mouse MIP-2), IL-8 receptor A and TNF-α were down-regulated in the VIP- versus PBS-treated cornea at 72 h p.i.; conversely, IL-10 receptor A was up-regulated. CCL23 (Mϕ inflammatory protein 3) was enhanced over 47-fold after VIP treatment, while mRNA expression of chemokine receptor 4 (CCR4) was down-regulated.
This translational pilot study using a non-human primate model for ocular infection indicates that: 1) P. aeruginosa-induced ocular infection is feasible; 2) disease response is similar to what is observed clinically and at the molecular level in the murine model; and 3) VIP treatment ameliorates disease pathogenesis.
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