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B. Manickam, P. Jha, P. S. Bora, N. S. Bora; Suppression of Experimental Autoimmune Anterior Uveitis (EAAU) by Recombinant Soluble Complement Regulatory Protein. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2646.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously shown that complement activation plays a critical role in the development of Experimental Autoimmune Anterior Uveitis (EAAU). This study was undertaken to explore the effect of recombinant soluble Crry, a complement regulatory protein on the disease activity in EAAU.
EAAU was induced in Lewis rats by immunization with bovine melanin associated antigen (MAA). The animals were divided into 3 groups. Group I received 1 mg of Crry-Ig by i.p. injection on days 9, 11 and 13. Group II received a similar injection of IgG2a (isotype control antibody) while the animals in Group III received sterile PBS alone at the above mentioned time points. Clinical and histopathological examination was used to determine the onset, duration and severity of the disease. Lewis rats (n= 3 /each group) were sacrificed at the peak of the disease. The eyes were harvested to determine the levels (both mRNA and protein) of C3 split products, C3aR, C5aR, IP-10, IFNγ, IL-10, ICAM-1, LECAM-1 and ß-actin by semi-quantitative RT-PCR and Western blot analysis.
Treatment with recombinant soluble Crry-Ig resulted in complete inhibition of EAAU while IgG2a and PBS treatment had no effect on the disease activity. The levels of C3 activation products were very low in the Crry-Ig treated group. Similarly, C3a receptor (C3aR) and C5a receptor (C5aR) were down-regulated in Crry-Ig treated group. The levels of cytokines (IFNγ and IL-10) and the adhesion molecules (ICAM-1 and LECAM-1) were also very low in these animals. In contrast, very high expression of all the above molecules was observed in IgG2a and PBS treated animals.
Our results demonstrate that the treatment with recombinant soluble Crry ameliorates EAAU. Our data further suggests that complement inhibition can be used as a suitable therapeutic approach to control inflammation and strengthens the case for using recombinant soluble Crry in the treatment of uveitis.
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