Complement System in Immunopathogenesis of Experimental Autoimmune Anterior Uveitis

Abstract

Abstract: : Purpose: To study the role of the complement system in experimental autoimmune anterior uveitis (EAAU). Methods: The role of the complement system in EAAU was explored by using cobra venom factor (CVF). EAAU was induced in two panels of Lewis rats (n=12/group) by immunization with bovine melanin associated antigen (MAA). In the experimental panel complement was depleted by a single injection of CVF (>30 units/rat, i.p.) given at day 9 post–immunization. Controls were injected with an equal volume of PBS. Clinical and histopathological examination was used to determine the onset, duration and severity of disease. Lewis rats (n=6/time point) were also sacrificed at day 8, 10, 12, 14, 16, 19, 23 and 30 post–immunization. Eyes were harvested at these time points for mRNA and protein analysis for TNF–α, IFN–γ , IL–10 and IP–10. Adhesion molecules (LECAM–1 and ICAM–1) were detected by immunoflourescent staining of the parafin sections of the eyes. Results: CVF treatment caused almost complete decomplementation, which lasted for 5 days in Lewis rats (naïve and MAA injected). The incidence of EAAU, the duration of the illness and severity of the disease (both clinical and histologic) were dramatically reduced in complement deficient (CVF treated) animals compared to controls (complement sufficient). CVF also suppressed the adoptive transfer EAAU. Using RT–PCR and ELISA we found that the presence of complement was critical for local production of IL–10, IFN–γ and IP–10. Both ICAM–1 and LECAM–1 were very strongly expressed on the iris and ciliary body of complement sufficient rats. However, both adhesion molecules were suppressed in CVF treated animals. Conclusions: Our results provide strong evidence that complement activation plays a central role in the immunopathogenesis of EAAU. These results suggest that targeting complement system may provide a new therapeutic approach for the treatment of uveitis.

Keywords: autoimmune disease • inflammation • uveitis-clinical/animal model