COMPARATIVE EFFICACY OF ANTIVIRAL DRUGS ON HUMAN OCULAR FIBROBLASTS

The effects of several antiviral drugs on fibroblast attachment and pr oliferation from human Tenon's capsule were investigated. These drugs included purine nucleoside analogs, vidarabine and acyclovir (ACV); py rimidine nucleoside analog, AZT; and a synthetic cyclic primary amine, amantadine. Fibroblast attachment and proliferation inhibition were d etermined by Coulter counter, a colorimetric assay of the enzyme hexos aminidase, and a H-3-thymidine uptake assay. Amantadine and AZT inhibi ted fibroblast attachment at concentrations higher than 6.61 x 10(-4) M and 3.73 x 10(-4) M, respectively. Amantadine and AZT had inhibitory effects on fibroblast proliferation as early as day 1, whereas vidara bine and ACV manifested their inhibitory effects after day three by Co ulter counter and hexosaminidase assays. For amantadine, AZT, ACV and vidarabine, the 50% inhibitory dose (ID50) were 4.94 x 10(-5) M, 1.26 x 10(-5) M, 4.60 x 10(-4) M, and 1.52 x 10(-5) M at day 9, respectivel y, as measured by H-3-thymidine uptake assay. All four antiviral agent s tested had inhibitory effects on human ocular fibroblast proliferati on and their inhibitory potential decreased in the order of amantadine greater than or equal to vidarabine > AZT greater than or equal to AC V. (C) 1995 Academic Press Limited