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J. Liu, M. Yu, N. S. Peachey, T. M. McIntyre; The Role of C3a Receptor and C5a Receptor in Maintenance of Retinal Function and Structure. Invest. Ophthalmol. Vis. Sci. 2010;51(13):484.
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The complement activation products C3a and C5a, interacting with C3a receptor (C3aR) and C5a receptor (C5aR), a family of G-protein couple receptors, play an important role in preventing cell apoptosis. This study investigates their role in retinal function.
C3aR-/-C5aR-/- (n=20), C3aR-/- (n=7), C3-/- (n=10) mice and their WT littermates from the age of 6 weeks up to 11 months old were studied. ERGs were used to analyze the function of the outer retina and retinal pigment epithelium (RPE). The histological changes of the retina were analyzed with H&E staining/light microscopy and electron microscopy. Tissue culture studies conducted using an RPE cell line (ARPE-19) examined the potential for complement proteins to modify apoptosis.
In comparison to WT, ERG a- and b- waves were significantly decreased in C3aR-/-C5aR-/-, C3aR-/-and C3-/-mice, as early as 6 weeks of age. RPE function was also decreased in C3aR-/-C5aR-/- and C3-/-animals. Electron microscopy showed the nuclei of RPE cells shrank in C3-/- and C3aR-/-C5aR-/- mice. Photoreceptor cells of both knockouts lost the normal structure of the outer segment discs. Complement activation fragment C5a prevented ARPE-19 mitochondrial apoptosis while C5aR antagonist induced ARPE-19 cell mitochondrial apoptotic pathway.
This study discovered that C3aR/C5aR deficiency impaired retinal function and structure, and suggests that these proteins play an important role in congenital or age-related retinal disease.
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