A Central Role for Sympathetic Nerves in Herpes Stromal Keratitis in Mice

作者：Yun Hongmin; Lathrop Kira L; Hendricks Robert L^*

来源：Investigative Ophthalmology & Visual Science, 2016, 57(4): 1749-1756.

DOI：10.1167/iovs.16-19183

• sympathetic nerves
• sensory nerves
• herpes stromal keratitis (HSK)
• herpes simplex virus type 1 (HSV-1)
• nerve degeneration
• cornea
• hyperinnervation

PURPOSE. Herpes simplex virus type 1 (HSV-1) is a neurotrophic virus that can cause herpes stromal keratitis (HSK), a severe corneal inflammation that can lead to corneal scarring and blindness. This study identified neurologic changes that occur in HSV-1-infected corneas and related them to HSV-1-induced immunopathology.
METHODS. Corneas of BALB/c and C57BL/6 mice were infected with HSV-1 strains that induce HSK. Changes in sensory nerves were identified by immunofluorescence staining of sensory and sympathetic nerves for substance P (SP) and tyrosine hydroxylase (TH), respectively, and confocal microscopic examination. Some mice received superior cervical ganglionectomy (SCGx) to eliminate sympathetic nerves from the cornea.
RESULTS. Normal corneas exclusively expressed sensory nerves that entered the stroma as large nerve stalks, branched to form a plexus at the epithelial/stromal interface, and extended termini into the epithelium. These nerves completely retracted from the infected cornea and were replaced by sympathetic nerves that sprouted extensively to hyperinnervate the corneal stroma but failed to form a plexus or extend termini into the epithelium. The hyper-innervating nerves expressed the sympathetic nerve marker TH and their invasion was blocked by performing SCGx. Moreover, the corneal opacity and neovascularization that normally characterizes HSK in this mouse model were largely abrogated by SCGx. Sensory nerves reinnervated infected corneas following SCGx, reformed a nerve plexus, and extended termini into the epithelium resulting in recovery of corneal sensitivity.
CONCLUSIONS. Sympathetic nerves have a central role in HSK in mice, preventing reinnervation by sensory nerves and promoting severe and persistent corneal inflammation.

• 出版日期2016-4