The Effects of Suramin in Combination with 5-Fluorouracil on the Proliferation of Human Retinal Pigmented Epithelial (HRPE) and Human Scleral Fibroblast (HScF) Cells
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Proliferative vitreoretinopathy (PVR) is a maladapted wound healing response of the retina which leads to a high rate of retinal redetachment after surgery. Human retinal pigmented epithelial (HRPE) and human scleral fibroblast (HScF) cells are important components in this disorder. As it is the proliferation and contraction of these cells that leads to PVR and redetachment, inhibition of their activities may lead to greater success rates in reattachment surgeries (Blumenkranz et aI, 1994). Suramin and 5-fluorouracil (5-FU) are two drugs that have been shown to have antiproliferative effects on these two cell types in vitro and in vivo. 5-FU is a drug that differs from uracil only by the substitution of a fluorine for a hydrogen on carbon-5 of uracil; thus, it is able to be substituted for uracil in all forms of RNA (Heidelberger, 1981). It is through this pathway that 5-FU acts to inhibit proliferation. Though it is not known precisely, suramin is thought to inhibit proliferation by binding various growth factors, and/or interfering with cell signal transduction. As suramin and 5-FU utilize different mechanisms for inhibiting proliferation, this study sought to test the anti proliferative effects of the two drugs in combination with each other on HRPE and HScF cells. Through the use of tissue culture it was found that, contrary to the hypothesis, the inhibitory effects of suramin and 5-FU were greater when tested alone versus in combination with one another. This might also mean that, in vivo, toxicity to normal cells surrounding the damaged areas will be increased with the administration of suramin and 5-FU in combination; yet it might have only negligible, or even antagonistic, effects on the inhibition of HRPE and HScF cell proliferation.
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