Effects of nucleoside antivirals and their metabolites on the corneal endothelium

The endothelial surface of rabbit corneas were perfused in vitro with bicarbonate Ringer's containing 5 mM glucose, 0.3 mM reduced glutathione, and various concentrations of nucleoside antivirals or their metabolites. During three hour perfusions, the swelling rates of corneas perfused with buffer containing either antivirals or metabolites were not significantly different from controls. Scanning electron microscopy of the endothelial cell layer revealed no structural abnormalities in any treatment group. One metabolite, fluoride ion, reduced endothelial glucose oxidation by about 60 percent when incubated with corneal tissue in vitro. The inhibition of glucose metabolism by fluoride ions was observed only at concentrations at least sixty times greater than would be anticipated in the anterior chamber of patients receiving topical F3TdR therapy. These studies indicate that 5-trifluoromethyl-2'-deoxyuridine, 5-iodo-2'-deoxyuridine, 9-(2-hydroxyethoxymethyl)-guanine, and their metabolites do not alter endothelial function when studied at physiological concentrations over a short term of exposure.