Purchase this article with an account.
Robin J. Goody, Michael Struharik, Steve Henry, Matthew S. Lawrence; Development Of A Nonhuman Primate Model Of Anterior Uveitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2944.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Uveitis accounts for 10% of blindness cases in the U.S., with idiopathic acute anterior uveitis considered the most prevalent. Several animal models have been devised to emulate the diverse clinical and immunological manifestations of uveitis but there is no definitive model for preclinical efficacy screening. The only disease model described in nonhuman primates, experimental autoimmune uveoretinitis induced by S-antigen immunization, produces extensive posterior pathology but has fewer anterior manifestations. Our objective was to develop a nonhuman primate model of anterior uveitis that provides reliable prediction of therapeutic efficacy in the clinic for novel candidate compounds.
Eight adult male African green monkeys (Chlorocebus sabaeus) were used in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Eyes were prescreened to confirm absence of ocular abnormalities. Following baseline slit-lamp exam, laser flare photometry and pachymetry, animals received bilateral intracameral injection of concanavalin A (con A) at doses of 10, 20 or 50µg or vehicle (sterile saline). Follow up ocular exams were performed 1, 2, 3 and 8 days later. Anterior chamber flare and cell was scored and clinical pathology recorded at each examination.
Con A induced peak laser flare within 24 hours of administration, with the 50µg dose eliciting maximal response. Laser flare resolved naturally over the following 7 days. Cell and flare scores, determined by slit-lamp exam, demonstrated a similar effect after con A delivery. Clinical pathology, including corneal edema, fibrin strands, iris neovascularization, synechiae, lens capsule cell and keratic precipitates was also most prominent in eyes receiving 50µg con A.
In this model con A induced transient anterior segment inflammation with classic pathologic indicators of anterior uveitis. Model validation with prototypic anti-inflammatory drugs and analysis of inflammatory signal cascades is required but this model already offers unique benefits over existing nonhuman primate models. The prominent anterior localization, short study duration, test species availability, and induction of a self-resolving disease state make this a good option for rapid preclinical efficacy and dose-optimization studies.
This PDF is available to Subscribers Only