Abstract
Purpose: :
Scleritis is a chronic inflammation that can be isolated to the eye, but occurs in the context of an immune-mediated systemic inflammatory condition, such as rheumatoid arthritis, in up to half of affected individuals. Type II collagen-induced arthritis (CIA) represents an animal model of autoimmune polyarthritis with similarities to human rheumatoid arthritis. We modified CIA models to determine whether scleritis-associated CIA occurs, and created a new model of anterior scleritis.
Methods: :
Male DBA/1J mice were immunized with bovine type II collagen (CII) emulsified in an equal volume of completed Freud’s adjuvant (CFA) intradermally at the tail base. At 21 days after first immunization, mice were challenged with CII emulsified in incomplete Freud’s adjuvant (IFA) intradermally at the tail base, back of the neck, or around the eye. Arthritis and the eyes were then observed and evaluated clinically and histologically. Eyes of CIA mice were assessed immunohistochemically at selected intervals after second immunization.
Results: :
CIA mice that received CII challenge at the tail base or back of the neck showed no evidence of inflammation in the eyes. Conversely, the anterior sclera of CIA mice that received CII challenge around the eye became markedly thicker than that of normal DBA/1J mice. The number of infiltrating cells in the anterior sclera of these mice was significantly higher than that of normal DBA/1J mice. Interestingly, no inflammation was found in the central cornea or posterior segment of mice that received CII challenge around the eye. In the modified CIA model, anterior scleritis developed at a later time point compared with arthritis, with severity of scleritis peaking after 2-3 weeks and inflammation remaining for more than 12 weeks.
Conclusions: :
We created a new model of auto-immune anterior scleritis associated with CIA. This model will be useful for investigating the immunopathology of human anterior scleritis associated with rheumatoid arthritis.
Keywords: autoimmune disease • sclera • inflammation