Chemical Sympathectomy Increases Sensitivity to Ocular HSV‐1 Infection

Abstract

We addressed the importance of sympathetic/parasympathetic innervation via chemical sympathectomy using the compound 6‐hydroxydopamine (6OHDA) in mice ocularly infected with herpes simplex virus type 1 (HSV‐1). The treatment of mice with 6OHDA (80 mg/kg, days ‐2, ‐1, and at the time of infection) was found to effectively eliminate or significantly reduce tyrosine‐hydroxylase‐staining nerves innervating the cornea. However, 6OHDA treatment had no impact on virus replication in the cornea or iris of mice at any time point evaluated post infection (pi). In contrast to the results found in the eye, 6OHDA treatment resulted in a time‐dependent increase in virus recovered in the trigeminal ganglia (TG) and brain stem (BS) of mice which was associated with increased mortality in comparison to vehicle‐treated controls. Ironically, there were no changes in leukocyte (myeloid and lymphoid) recruitment to the cornea, TG, BS, or draining lymph nodes (mandibular and deep cervical) of 6OHDA‐treated mice in comparison to controls during acute infection (day 3‐day 7 pi). Moreover, there was no change in the development or activity of CTLs in the draining lymph nodes or infected tissue of 6OHDA‐treated mice. Currently, measurement of cytokine levels in the nervous system is underway to determine if levels offer an explanation for the increased sensitivity to infection in the 6OHDA‐treated mice.