Recent studies have suggested that
reagents inhibiting complement activation could be effective in treating T cell mediated
autoimmune diseases such as autoimmune
uveitis. However, the precise role of the
complement anaphylatoxin receptors (C3a and
C5a receptors) in the pathogenesis of autoimmune
uveitis remains elusive and controversial. We induced experimental autoimmune
uveitis in mice deficient or sufficient in both C3a and
C5a receptors and rigorously compared their
retinal phenotype using various imaging techniques, including indirect ophthalmoscopy, confocal scanning
laser ophthalmoscopy, spectral domain optical coherence tomography, topical endoscopic fundus imaging, and histopathological analysis. We also assessed
retinal function using electroretinography. Moreover, we performed Ag-specific T cell recall assays and T cell adoptive transfer experiments to compare pathogenic T cell activity between wild-type and knockout mice with experimental autoimmune
uveitis. These experiments showed that C3a
receptor/C5a receptor-deficient mice developed much less severe
uveitis than did control mice using all
retinal examination methods and that these mice had reduced pathogenic T cell responses. Our data demonstrate that both
complement anaphylatoxin receptors are important for the development of experimental autoimmune
uveitis, suggesting that targeting these receptors could be a valid approach for treating patients with autoimmune
uveitis.