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D. A. Copland, K. Hussain, S. Baalasubramanian, C. J. Calder, B. P. Morgan, L. B. Nicholson, A. D. Dick; The Role of Complement in Experimental Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1995.
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To determine the influence of the blockade of the complement component C5 on disease progression and severity in Experimental Autoimmune Uveoretinitis (EAU).Background: The murine model of human inflammatory eye disease, EAU, is characterized by structural retinal damage mediated by infiltrating macrophages. Activation of complement is an important factor in the inflammatory disease process. The cleavage of C5 into fragments C5a and C5b is a critical event during the complement cascade. C5a is a potent pro-inflammatory agent that induces cell migration, cell adhesion and the release of cytokines. Therapeutic approaches to prevent inflammation include the use of blocking monoclonal antibodies (mAb) to prevent C5 cleavage.
EAU was induced in B10.RIII mice by immunization with hRBP-3161-180 and disease was assessed by histological scoring. Some experimental groups received anti-C5 mAb intraperitoneally as a therapeutic intervention on days 5 and 10 following EAU induction, other groups also received an additional pre-treatment 1 day prior to immunization. Similar groups of control mice received only PBS at these times.
The effect of systemic treatment with anti-C5 mAb, whether administered pre- or post- immunization results in significantly reduced disease scores as compared with PBS control groups.
The activation of C5 in the complement cascade is an important factor to the initiation and/or development of EAU. These experiments demonstrate that systemic administration of anti-C5 mAb in vivo either pre- or post-disease immunization suppresses EAU. Therefore, blocking C5 activation demonstrates therapeutic potential to protect against tissue damage during autoimmune responses in the retina.
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