title: A Central Role for Sympathetic Nerves in Herpes Stromal Keratitis in Mice.
abstract: OBJECTIVE
  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 hyperinnervating 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.
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Yun
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States 2Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
authors.forename: Kira L
authors.initials: KL
authors.lastname: Lathrop
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States 3Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 4Department of Microbiology and Molecular Geneti.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hendricks
mesh_terms: D000818:Animals; D001767:Blinking / Q000502:physiology*; D002572:Cervical Plexus / Q000503:physiopathology* / Q000601:surgery / Q000821:virology; D003319:Corneal Stroma / Q000294:innervation* / Q000473:pathology; D004195:Disease Models, Animal; D015828:Eye Infections, Viral / Q000473:pathology* / Q000503:physiopathology / Q000821:virology; D005260:Female; D015171:Ganglionectomy; D018259:Herpesvirus 1, Human / Q000472:pathogenicity; D007150:Immunohistochemistry; D016849:Keratitis, Herpetic / Q000473:pathology* / Q000503:physiopathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D010784:Photomicrography; D012720:Severity of Illness Index; D013564:Sympathetic Nervous System / Q000503:physiopathology* / Q000821:virology; D014741:Video Recording