Timolol promotes reactivation of latent HSV-1 in the mouse iontophoresis model.

The present study examined the effect of topical timolol, a nonspecific beta 1 and beta 2 blocker on reactivation and ocular shedding of latent HSV-1 in an improved mouse iontophoresis model. Latent trigeminal ganglionic infection was established in Balb/C mice following inoculation by corneal scarification with HSV-1 W strain, a clinical isolate, and confirmed by co-cultivation. On day 30, postinfection (pi), the mice were divided into two groups, and treatment begun with coded eye drops (timolol 0.5% or placebo) BID OU for 5 days. On day 31 pi, iontophoresis with 1% 6-hydroxydopamine was performed, and daily treatment with topical epinephrine and 1% prednisolone was administered. Reactivation and recovery of latent HSV-1 was determined by daily ocular swabs, and characteristic HSV-1 cytopathic effect in Vero cells. Results demonstrated that the timolol-treated group had a significantly greater number of positive eyes, multiple shedding episodes, and total shedding days compared to the control group. We conclude that beta blockade promotes recurrent ocular shedding induced by epinephrine in the mouse iontophoresis latency model.