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Abstract
The complement system has been increasingly implicated in the pathophysiology of autoimmune disease. Complement expression in the normal human eye had not been previously completely defined. We performed immunohistochemical studies for membrane complement proteins in normal human retina to provide a baseline for future studies. We found expression of the anaphylatoxin receptors, CD55, and CD59 in the inner retina and CD46 in a polarized fashion on the retinal pigment epithelium.
Previous studies in uveitis have shown activated fragments of complement in human eyes with uveitis and animal models have shown an effect on disease by complement depletion with cobra venom factor. Experimental autoimmune uveitis (EAU) is an animal model of posterior uveitis. We sought to determine the role of complement in EAU using complement altered mice. We induced EAU in mice deficient in C3, the central complement component. These mice showed a marked reduction in both the incidence and severity of disease. EAU in mice producing a soluble inhibitor of complement activation in the eye also revealed a reduced incidence and severity of disease. Having established that lack of or inhibition of the central complement activation pathway results in reduced disease, we next sought to determine which of the downstream mediators of complement function was responsible for this effect. EAU in mice deficient for each of the anaphylatoxin receptors individually and for C5 produced no differences in disease compared to wild type controls. C5 deficient animals are incapable of producing either C5a or the membrane attack complex, a pore forming structure that disrupts homeostasis. Thus it is unclear at this point which complement mediator is responsible for the proinflammatory effects of complement activation in EAU. It seems probable that redundancy exists in the system, most likely in the anaphylatoxin system, with either anaphylatoxin's presence with its receptor sufficient for the needed proinflammatory effects on EAU.
