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Corneal nerves are necessary for adrenergic reactivation of ocular herpes
D S Rootman1, Y Haruta, J M Hill
1LSU Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans 70112-2234.
Abstract:
Herpes simplex virus type 1 (HSV-1) can infect the cornea and achieve ganglionic latency. HSV-1 can later be activated by a variety of effectors although the exact mechanism of reactivation is unknown. Rabbits harboring latent HSV-1 strain McKrae can be induced to shed virus by ocular iontophoresis of epinephrine to the cornea. No studies have been done to investigate if corneal nerves are necessary for epinephrine induction of HSV-1 ocular shedding. We did penetrating keratoplasty (PKP) in one eye each of 23 rabbits; the other eye served as an unoperated control. The surgery effectively denervates the area of the transplant for up to 90 days. Eighteen rabbits carrying latent HSV-1 strain McKrae received corneas from uninfected rabbits. Five uninfected rabbits with no latent virus received corneas from rabbits harboring latent HSV-1. On days 10-14 after penetrating keratoplasty, 24 eyes in the HSV-1 latent group and all ten uninfected eyes received iontophoresis of 0.01% epinephrine (0.8 mAmps for 8 min or 0.6 mAmps for 6 min) once daily for 3 days by means of an eye cup whose diameter was less than the diameter of the transplant. Six rabbits in the HSV-1 latent group received intravenous injections of cyclophosphamide (75 mg/kg) and dexamethasone (4 mg/kg). Following iontophoretic or immunosuppressive induction, the eyes were swabbed daily for 9 days. Of the 12 rabbits with latent virus which were treated by iontophoresis, one of the transplanted eyes and eight of the nontransplanted eyes were induced to shed virus. The mean duration of shedding in the nontransplanted eyes was 3.25 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Corneal nerves are not essential for epinephrine to induce herpes simplex virus type 1 (HSV-1) reactivation and shedding. This study shows that even denervated corneas can shed HSV-1 after epinephrine treatment.
Area of Science:
- Ophthalmology
- Virology
- Immunology
Background:
- Herpes simplex virus type 1 (HSV-1) establishes latency in corneal ganglia.
- Reactivation mechanisms of latent HSV-1 are not fully understood.
- Epinephrine can induce HSV-1 shedding in rabbits, but the role of corneal nerves is unknown.
Purpose of the Study:
- To investigate if corneal nerves are necessary for epinephrine-induced HSV-1 ocular shedding.
- To determine the role of denervation in HSV-1 reactivation.
Main Methods:
- Penetrating keratoplasty (PKP) was performed on rabbit corneas to create denervated areas.
- Rabbits with latent HSV-1 were treated with ocular iontophoresis of epinephrine.
- Immunosuppression with cyclophosphamide and dexamethasone was also used in some rabbits.
- Ocular shedding of HSV-1 was monitored daily after treatment.
Main Results:
- One of 12 transplanted (denervated) eyes shed HSV-1 after iontophoresis.
- Eight of 12 nontransplanted (innervated) eyes shed HSV-1 after iontophoresis.
- The mean duration of shedding in nontransplanted eyes was 3.25 days.
Conclusions:
- Corneal nerves are not required for epinephrine to induce HSV-1 reactivation and shedding.
- Denervation of the cornea does not prevent HSV-1 shedding induced by epinephrine.
- Further research is needed to elucidate the precise mechanisms of HSV-1 reactivation.