Migration of retinal pigment epithelial cells in vitro modulated by monocyte chemotactic protein-1: enhancement and inhibition

Abstract.

Background: The migration of retinal pigment epithelial (RPE) cells is an initial step in the development of proliferative vitreoretinopathy (PVR). This in vitro study was carried out to investigate the effects of monocyte chemotactic protein-1 (MCP-1) on the migration and proliferation of RPE cells. Methods: We used an in vitro wound healing model in which a small area of a confluent monolayer of human RPE (HRPE) cells was denuded with a razor blade. The cultures were subsequently incubated with MCP-1, IL-1β, TNF-α, or combinations thereof. Neutralizing IgG₁ of anti-human MCP-1, dexamethasone (DEX) or daunorubicin were also added to the cultures to test their inhibitory effects on migration of RPE cells. HRPE migration was measured as the number of cells that entered the denuded area. The effect of MCP-1 on proliferation of HRPE cells was examined by MTT assay. Results: MCP-1 stimulated HRPE cell migration in a dose-dependent manner. IL-1β or TNF-α slightly stimulated HRPE cell migration, but adding anti-MCP-1 IgG1 significantly reduced this effect. MCP-1-induced migration could be inhibited by DEX but not by daunorubicin. MCP-1 did not show a significant effect on HRPE cell proliferation. Conclusion: MCP-1 stimulates HRPE cell migration, suggesting that this chemokine regulates the development of PVR at the initial stage. The migration of HRPE cells induced by IL-1β and TNF-α may be associated with the MCP-1 that HRPE cells secretes under the stimulation of these two cytokines. The knowledge that MCP-1-induced migration of HRPE cells is inhibited by DEX may be useful in devising an effective treatment for PVR.