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.
Rootman
D S
DS
Lions Eye Research Laboratories, Louisiana State University Eye Center, New Orleans 70112-2234.
Haruta
Y
Y
Hill
J M
JM
D000818:Animals; D004195:Disease Models, Animal; D004837:Epinephrine / Q000008:administration & dosage / Q000009:adverse effects; D006892:Hydroxydopamines / Q000008:administration & dosage / Q000009:adverse effects; D007478:Iontophoresis / Q000009:adverse effects*; D007635:Keratitis, Dendritic / Q000382:microbiology*; D012453:Saimiri; D018139:Simplexvirus / Q000254:growth & development* / Q000302:isolation & purification; D013566:Sympathomimetics / Q000008:administration & dosage / Q000009:adverse effects*; D013999:Timolol / Q000008:administration & dosage / Q000009:adverse effects; D014775:Virus Activation / Q000187:drug effects*
D006892:Hydroxydopamines; D013566:Sympathomimetics; D013999:Timolol; D004837:Epinephrine