Reactivation of HSV-1 in primates by transcorneal iontophoresis of adrenergic agents.

Transcorneal iontophoresis of adrenergic agents has been shown to reactivate latent herpes simplex virus type 1 (HSV-1) and to produce viral shedding in the tear film in rabbits and mice, but not, to date, in nonhuman primates. In this study, we demonstrated induced reactivation of latent HSV-1, viral shedding, and production of ocular lesions in nine squirrel monkeys (Saimiri sciureus) by iontophoresis of 6-hydroxydopamine (6-HD) with topical instillation of epinephrine or with iontophoresis of timolol. Monkey corneas were scarified and inoculated with McKrae strain HSV-1 on three separate occasions. All monkeys received daily intramuscular prednisolone for 39 or 46 days prior to ionotophoresis. Once latency was established, a single ionotphoresis of 6-HD was performed on both eyes in five of the monkeys, followed by 1% epinephrine given topically four times daily for 5 days. Iontophoresis of timolol was performed on both eyes in the other four monkeys once per day on 3 consecutive days. Eight of the ten eyes receiving 6-HD and epinephrine shed HSV-1; seven eyes developed deep punctate, dendritic, or geographic corneal lesions. Seven of the eight eyes receiving timolol shed HSV-1; six of the eyes developed lesions suggestive of HSV-1 specific corneal lesions. The methods used in this report were slightly different from those used to reactivate HSV-1 in rabbits, in that repeated inoculations with HSV-1 and repeated intramuscular injections with prednisolone were required; however, these results demonstrate that iontophoresis of adrenergic agents can produce shedding and recurrent epithelial lesions in the nonhuman primate.