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I Nachbar, F Sistani, UH Steinhorst; Migration And Proliferation Of Human Retinal Pigment Epithelial Cells Induced By Alteration Of Protein Kinase C Activity On Different Extracellular Matrices . Invest. Ophthalmol. Vis. Sci. 2002;43(13):691.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Rentinal pigment epithelium-loss is a part of the pathological process in age-related macular degeneration (ARMD). A potential therapeutic option might be to stimulate migration of human retinal pigment epithelial cells (hRPE) from the periphery to the damaged macular area. We investigated the migration of hRPE cells induced by alteration of protein kinase C activity (PKC) using various extracellular matrices (ECM). Methods: The effect of phorbol 12-mystriate 13-acetate (PMA) as an PKC activator and staurosporine as an PKC inhibitor on hRPE cell migration was investigated in vitro on different ECMs (glass, fibronectin and collagen type IV). After 24h, cell migration was measured by counting those cells that had entered a previously denuded area of the slide. All cultures were exposed to proliferating cell nuclear antigen (PCNA) using the APAAP-technique, permitting to identify proliferation activity. Results: Staurosporine reduced the number of hRPE cells entering the denuded area significantly (p< 0,05) compared with controls. In contrast PMA increased the number of migrating hRPE cells on collagen type IV. However, no such effect was found on glass or fibronectin. Conclusion: Activated PKC increases migratory activity of hRPE cells in vitro. This effect depends of the type of ECM on which the cells are grown. However, in our experimental settings proliferation always played an essential role in wound healing which was independent of the PKC activity or ECM. None of the substances used, stimulated migration of hRPE cells without simultaneously increasing cell proliferation.
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