A complement receptor C5a antagonist regulates epithelial to mesenchymal transition and crystallin expression after lens cataract surgery in mice

PURPOSE: To evaluate the effects of complement employing a mouse model for secondary cataract. METHODS: The role of complement receptor C5a (CD88) was evaluated after cataract surgery in mice. An antagonist specific to C5a receptor was administered intraperitoneally to mice. Epithelial to mesenchymal transition (EMT) was evaluated by alpha-smooth muscle actin (α-SMA) staining and proliferation by bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU) incorporation. Gene expression patterns was examined by microarray analysis and quantitative polymerase chain reaction (QPCR). RESULTS: We found that administration of a C5aR antagonist in C57BL/6J mice decreases EMT, as evidenced by α-SMA expression, and cell proliferation. Gene expression by microarray analysis reveals discreet steps of gene regulation in the two major stages that of EMT and lens fiber differentiation in vivo. A hallmark of the microarray analysis is that the antagonist seems to be a novel stage-specific regulator of crystallin genes. At week two, which is marked by lens fiber differentiation genes encoding 12 crystallins and 3 lens-specific structural proteins were severely down-regulated. CONCLUSIONS: These results suggest a possible therapeutic role of an antagonist to C5aR in preventing secondary cataracts after surgery. Also these results suggest that crystallin gene expression can be regulated by pro-inflammatory events in the eye.