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M. M. Jann, H. L. Rosenzweig, S. R. Planck, T. M. Martin, T. T. Glant, M. P. Davey, J. T. Rosenbaum; Anterior Uveitis Accompanies Joint Disease in a Murine Model of Ankylosing Spondylitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):191. doi: https://doi.org/.
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Ankylosing spondylitis (AS) is the most common systemic disease associated with uveitis in Europe and North America. Although the joint manifestations of AS can be mimicked in several animal models, uveitis is not a reported feature. Here we sought to assess whether ocular inflammation occurs in a previously described murine model of proteoglycan-induced arthritis (PGIA), wherein mice develop progressive sacroiliitis, spondylitis and peripheral arthritis as occurs clinically in patients with AS.
Female, BALB/c mice or mice that are transgenic for the T cell receptor specific for a dominant arthritogenic epitope of cartilage proteoglycan (TCR-Tg mice) were immunized intraperitoneally with purified human cartilage proteoglycan (PG) in the presence of the adjuvant dimethyl-dioctadecyl ammonium bromide (DDA). The ocular inflammatory response was assessed by intravital microscopy and the number of rolling, adherent and infiltrating cells within the iris was quantified.
Due to the increased CD4+ T cell population reactive to PG, the TCR-Tg mice exhibited increased incidence and severity of joint disease compared to immunized wild-type BALB/c mice. While the BALB/c mice showed minimal increase in the iris intravascular inflammatory response at 12 weeks post immunization, the TCR-Tg mice showed a significant increase in the incidence and severity of uveitis as measured by the number of rolling, adhering and infiltrating cells within the iris compared to adjuvant-control mice. We have begun to characterize the kinetics of ocular inflammation in the TCR-Tg mice immunized with PG and have observed a significant increase in rolling and adhering cells within 2 weeks post immunization (a time prior to measurable peripheral arthritis). The intravascular inflammation tends to improve at 4 weeks post immunization, but it is increased again at 10 and 12 weeks post immunization, suggestive of episodic inflammation.
There is a strong relationship between uveitis and AS in patients. Our observation that uveitis occurs concomitantly with spondylitis in a mouse model may prove to be valuable tool for investigation of mechanisms involved in a common clinical form of uveitis. In addition, the observations suggest that proteoglycan is a potential autoantigen in AS.
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