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Laura Belen, Kortni Violette, Jennifer Brackett, Andy Whitlock; Validation of the Anterior Chamber Paracentesis Model for the Screening of Novel Ophthalmic Anti-Inflammatory Drug. Invest. Ophthalmol. Vis. Sci. 2013;54(15):110.
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The development of novel anti-inflammatory drugs for treatment of inflammatory conditions such as dry eye, chronic allergy, blepharitis, uveitis, or ocular trauma is complicated by the lack of a preclinical model with a robust, consistent inflammatory response. The anterior chamber paracentesis model (ACP) is an acute animal model of ocular inflammation that involves the breakdown of the blood aqueous barrier and subsequent release of proteins and PGE2 into the aqueous humor (AH). PGE2 up-regulation is a common factor of many ocular surface diseases such as dry eye, chronic allergy, and blepharitis. The purpose of this study was to benchmark numerous classes of anti-inflammatory drugs (steroids, NSAIDs, and cyclosporine) in an ACP model to determine if it could serve as a surrogate for ocular surface inflammation.
Inflammation was induced in NZW rabbits by aspirating 100 µL of AH from the anterior chamber. The extent of inflammation was assessed 2 hours following the challenge by slit lamp and post-life biochemical analysis of AH for protein exudates by BCA assay and PGE2 levels by ELISA. Anti-inflammatory drugs tested included Dexamethasone (Dex), Prednisolone (Pred), Keterolac, Bromfenac, and Restasis. Balanced saline was used as a vehicle control. Four animals (8 eyes) per treatment were dosed bilaterally four times daily one day prior to ACP. On the day of AH collection, animals had a clinical observation and received topical treatment 3, 2, 1 and .5 hours prior to the first AH collection. Animals received topical treatment 30, 60 and 90 minutes post first collection.
Only bromfenac and ketorolac significantly reduced AH protein exudates in the NZW rabbits following ACP compared to vehicle control (p < .01). Dex, bromfenac and keterolac statistically decreased PGE2 levels compared to vehicle control (p < .01, p < .05, p< .05). Dex and Restasis also resulted in decreased levels of PGE2 release, but the decrease was not statistically significant.
Both steroids and NSAIDs appear to be efficacious in this model. While not significant, Restasis had some efficacy that may be increased by adjusting the power of the study. The results of this study indicate that ACP could serve as a surrogate model for ocular surface inflammation and help further novel drug discovery for indications such as dry eye and belpharitis.
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