Characterization of a Chronic Panuveitis Model in the Rabbit
David Culp, PhD
David Culp, Justin Prater, Adam Moser, Brian C. Gilger
Powered Research, Research Triangle Park, NC, United States
Clinical Sciences, North Carolina State University, Raleigh, NC, United States
Purpose: To characterize a sensitive and translatable model of chronic panuveitis in the New Zealand White rabbit (NZW).
Methods: Rabbits were immunized subcutaneously with 10 mg of Mycobacterium tuberculosis (MTB), H37Ra antigen in incomplete Freund’s adjuvant. Seven days later they were boosted with 10 mg of H37Ra antigen in phosphate buffered saline. The left eyes were challenged intravitreally (IVT) 2 weeks later with 33 µg of antigen in balance salt saline (BSS). On the same day of challenge animals were given bilateral intravitreal injections of triamcinolone acetonide (TA) or BSS. Slit lamp biomicroscopy (Hackett-McDonald [HM] ocular inflammatory scores) were evaluated on days 1, 3, 7, 14, 21, and 28. After euthanasia, eyes were collected, fixed, sectioned, stained with H&E, and examined by light microscopy.
Results: Panuveitis was evident within 24 hours in eyes receiving the intravitreal challenge of H37Ra antigen. Cumulative HM scores were significantly lower (P<0.05) in eyes treated with TA compared to BSS injected eyes by day 1, and remained lower throughout the course of the study. By day 14, HM scores in the TA treated eyes returned to baseline. Ocular inflammation peaked on day 1 in BSS treated eyes and remained elevated throughout the course of the study. Histologic scores were consistently lower in TA treated eyes compared to control BSS injected eyes. Furthermore, inflammation was evident on histology in both the posterior and anterior segments.
Conclusions: In this chronic H37Ra uveitis model, we demonstrated that intravitreal TA significantly reduced ocular inflammation compared to control treated eyes. This chronic, panuveitis model, and the described semi-quantitative clinical and histologic assessment, promises to be a valuable model for evaluation of novel drugs or delivery methods designed to treat intraocular inflammatory diseases.
W. David Culp: Commercial Relationship (Employee)
Adam Moser: Commercial Relationship (Employee)
Justin Prater: Commercial Relationship (Employee)
Brian Gilger: Commercial Relationship; Powered Research:(Consultant)