RETINAL-PIGMENT EPITHELIAL-CELLS - AUTOCRINE AND PARACRINE STIMULATION OF EXTRACELLULAR-MATRIX CONTRACTION

Background: This study was carried out to examine the biological activ ity of contraction promoters produced by dedifferentiating retinal pig ment epithelial cells (RPE) and to evaluate the importance of autocrin e and paracrine effects within a semi-closed environment like the vitr eal cavity. Methods: RPE at different stages of dedifferentiation in c ulture were examined for their ability (a) to generate tractional forc es in vitro, with and without serum stimulation, and (b) to produce an d release contraction-stimulating proteins. Autocrine versus paracrine effects of cell-secreted promoters were tested by using RPE or human dermal fibroblasts (HDF) as target cells. The contraction-stimulating activity of the cell-secreted promoters was partially characterized an d compared to the activity of defined promoters. Results: Our study co nfirmed that RPE can synthesize and secrete cell-contraction-promoting factor(s) active in stimulating the development of tractional forces by RPE as well as HDF. The quantity of biological activity secreted pe r cell decreases with progressive dedifferentiation, yet the responsiv eness of the cell to contraction promoters increases. The contraction promoter(s) synthesized by RPE is partially distinct from the promoter s in serum, TGF-beta 1 and beta 2, IGF-1, ET-1 and PDGF. The contracti on-promoting effects of the RPE product(s) can be completely blocked b y staurosporine. Conclusion: Dedifferentiation of RPE is characterized by increasing capacity to generate tractional forces and decreasing s ynthetic capacity. RPE within a semi-closed system like the vitreal ca vity can, theoretically, act both as promoting and active component of traction-related events (tractional retinal detachment).