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Abstract
PURPOSE: To examine the potential of a broad-spectrum kinase inhibitor as a means of neutralizing the effects of contraction promoters on ocular cells. METHODS: The inhibitory effects of a broad-spectrum kinase inhibitor were examined and characterized using an in vitro assay of extracellular matrix contraction by choroidal fibroblasts. RESULTS: Staurosporine effectively inhibited collagen matrix contraction by choroidal fibroblasts. The inhibitory effects of staurosporine were rapid in onset and reversible upon removal of the inhibitor. Inhibition was observed when fibroblasts were stimulated with serum, transforming growth factor beta 1, transforming growth factor beta 2, platelet-derived growth factor, and endothelin-1. We also observed that platelet-derived growth factor and endothelin-1 stimulated only modest amounts of matrix contraction compared to transforming growth factor beta. CONCLUSIONS: Matrix contraction by cells, as observed in the development of tractional forces, can be modulated by a broad-spectrum kinase inhibitor. The marginal contractile responses of choroidal fibroblasts to platelet-derived growth factor and endothelin-1, both potent promoters of dermal fibroblast contraction, suggest that there are substantive difference in the responses of these two cell types to growth factors.