Selection of Therapeutic Agents for Intraocular Proliferative Disease

We confirm the potent antiproliferative effects of the fluoropyrimidines on cellular proliferation in vitro in three different nonmalignant cell types. All fluoropyrimidines tested, except for fluorocytosine, decrease proliferation of human dermal fibroblasts, bovine aortic vascular endothelial cells, and human retinal pigment epithelial cells in vitro. Fluorouridine, an intracellular metabolite of fluorouracil, is nearly 100-fold more potent than fluorouracil and its deoxymetabolite. Human dermal fibroblasts are more sensitive to the inhibitory effects of deoxymetabolites than the cells of either human retinal pigment epithelium or bovine aortic vascular endothelium. Fluorouridine and other fluoropyrimidines may prove to be valuable second-generation drugs in the treatment of intraocular proliferative disorders.