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M. Ni, K. Lalwani, G. De Vries; An Optimized Experimental Panuveitis Model in Rabbit. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5160.
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Several experimental Uveitis animal models have been developed and used in anti-inflammatory drug discovery and research on the mechanism of action of autoimmune diseases over the past twenty years. However, no optimized model exists which allows both the direct observation of the progress of intraocular inflammation or ocular tissue damage and which aids in developing intraocular drug delivery devices. The goal of this study is to identify and characterize a suitable experimental panuveitis model in rabbit that can be easily used to rapidly screen sustained-release devices containing anti-inflammatory or autoimmune-inhibitory compounds.
Sixty Dutch Belted rabbits were immunized twice subcutaneously with 10 mg of Mycobacterium Tuberculosis H37Ra antigen on day 0 and day 7. Rabbits were randomized into 10 groups of 4-8 each. All right eyes were challenged with an intravitreal injection of 100 µl antigen in 0.9% saline at a dose ranging from 0.05 to 50 µg. Control eyes received 100 µl of vehicle. All study eyes were examined with a Slit Lamp and Fundus Camera on days 1, 3 and 7, followed by a once-a-week or bi-weekly up to 10 weeks. The severity of the intraocular inflammation or eye tissue damage was evaluated using standard grading scales for anterior and posterior segment inflammation. Lastly, rabbits were euthanized at designated time points, eyes were enucleated for histology.
Clinical observation and laboratory measurement showed that 1-3 µg antigen/eye induced an optimized panuveitis disease with signs of intraocular inflammation and ocular tissue damage. Intraocular inflammation (flare and cells in the aqueous humor, iris/lens adhesion, iritis, vitritis, and retinitis) occurred one day after the intravitreal antigenic challenge, reached its peak at one week, and then subsided two weeks later. Progressive ocular tissue damage (irregular pupils, cataract, proliferative retinopathy, and choroiditis) started two weeks after the intravitreal antigenic challenge, and remained during the 70-day observation period.
The disease developing mechanism, clinical signs and features, and time course of this panuveitis model are similar to paunuveitis in humans. Unlike other models, this rabbit panuveitis permits the direct observation of disease progression and can be used to screen anti-inflammatory drugs and to evaluate the pathophysiology of autoimmune disease. Furthermore, large rabbit eyes allow more flexibility in evaluating alternate routes for administering sustained-release drug delivery systems for the treatment of ocular diseases localized in the anterior or posterior segments of the eye.
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