Inflammation in Autoimmune Uveitis is Controlled by Complement Regulatory Proteins

Abstract

Abstract: : Purpose: To explore the role of the complement system and complement regulatory proteins in intraocular inflammation in experimental autoimmune anterior uveitis (EAAU). Methods: The role of the complement system in EAAU was explored using neutralizing monoclonal antibodies against complement regulatory proteins in the rat, Crry and CD59. EAAU was induced in two panels of Lewis rats (n=6) by immunization with bovine melanin associated antigen (MAA). In the experimental panel, monoclonal antibody against rat Crry (125 ug) or CD59 (250 ug) was administered (i.v.) separately (once only) on day 9, day 14 or day 27 post-immunization. Controls were injected with an equal amount of normal mouse IgG (isotype control). Clinical and histopathological examination was used to determine the onset and severity of disease. Lewis rats were sacrificed at three clinical stages of the disease: at the clinical onset of inflammation, at the peak of disease and after resolution. Results: Animals treated with anti-Crry or anti-CD59 on day 9, developed EAAU 3 days earlier than controls. Additionally, the duration and severity of the disease was increased . Antibody injection on day 14 did not alter the onset of EAAU; however, EAAU was prolonged and the disease was more severe. Injection of anti-Crry or anti-CD59 during resolution (day 27) had no effect on EAAU. Conclusions: Inhibition of the complement regulatory proteins prior to the onset of EAAU resulted in the early onset of disease, greater severity and delayed resolution. Thus, the course of autoimmune uveitis is controlled, in part, by the complement system.

Keywords: autoimmune disease • immunomodulation/immunoregulation • uveitis-clinical/animal model