Suppression of Complement Regulatory Proteins Exacerbates Experimental Autoimmune Anterior Uveitis (EAAU)

Abstract

Purpose: : To study the in vivo role of complement regulatory proteins (CRPs) in experimental autoimmune anterior uveitis (EAAU).

Methods: : Lewis rats immunized with melanin associated antigen (MAA) received a single i.v. injection of anti–rat Crry, anti–rat CD59 or a combination of anti–Crry and CD59 on day 9, 14, 19 or 27 post–immunization. Controls were injected with normal mouse IgG (isotype control). In a separate experiment MAA injected animals received a single i.v. injection of anti–sense oligonucleotide (AS–ODN) against Crry or CD59 at above mentioned time points. Control group received a similar treatment with sense oligonucleotides. Additional group of MAA immunized Lewis rats received single i.v. injection of a mixture of siRNA against Crry and CD59 while control animals received a similar treatment with control siRNA. Clinical and histopathological examination was used to determine the onset, duration and severity of disease.

Results: : Suppression of Crry in vivo at days 9, 14 and 19 by neutralizing mAb or AS–ODN resulted in early onset of disease, exacerbation of intraocular inflammation as well as delayed resolution of uveitis. In contrast, CD59 antibodies and ODN were effective only when given before the onset of EAAU. However, the most profound effect on the disease was observed when a mixture of Crry and CD59 mAbs or AS–ODN was administered intravenously. Similar effect was observed when a combination of Crry and CD59 siRNA was used. Interestingly, there was no permanent histologic damage to ocular tissue after the inflammation cleared in these animals.

Conclusions: : In conclusion, our study demonstrates the in vivo role of ocular CRPs in protecting autologous tissue from injury induced by complement activation during autoimmune uveitis.

Keywords: autoimmune disease • inflammation • uvea