title: Confocal Microscopic Analysis of a Rabbit Eye Model of High-Incidence Recurrent Herpes Stromal Keratitis.
abstract: OBJECTIVE
  Using CJLAT, a chimeric herpes simplex virus (HSV-1) that produces a high incidence of herpes stromal keratitis (HSK) in latently infected rabbits, and in vivo confocal microscopy (CM), we characterized the cellular events that precede the development of HSK.
  
  
  METHODS
  Thirty days after infection, in vivo CM was performed daily for 10 days and then weekly for up to 80 days after infection.
  
  
  RESULTS
  We detected 3 types of subclinical corneal lesions before HSK was clinically apparent: (1) small epithelial erosions; (2) regenerating epithelium overlying small cell infiltrates within the basal epithelial cell layer; and (3) dendritic-like cells within the basal epithelial layer overlying stromal foci containing infiltrating cells. Sequential in vivo CM observations suggested that subclinical foci resolved over time but were larger and more abundant with CJLAT than with wild-type HSV-1 McKrae. Active HSK was observed only with CJLAT and was initially associated with a large epithelial lesion overlying stromal immune cell infiltrates.
  
  
  CONCLUSIONS
  These results suggest that replication in the cornea of reactivated virus from the trigeminal ganglia produces epithelial lesions, which recruit immune cell infiltrates into the basal epithelial layer and anterior stroma. The virus is usually cleared rapidly eliminating viral antigens before the arrival of the immune cells, which disperse. However, if the virus is not cleared rapidly, or if an additional reactivation results in an additional round of virus at the same site before the immune cells disperse, then the immune cells are stimulated and may induce an immunopathological response leading to the development of HSK.
authors.affiliation: *Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA; †Department of Biomedical Engineering, University of Irvine, Irvine; ‡Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan; §Cellular and Molecular Immunology Laboratory, University of California Irvine, Irvine, CA ¶Institute for Immunology, University of California Irvine, Irvine, CA ‖Department of Microbiology and Immunology, National Cheng Kung University, Tainan Taiwan; **School of Veterinary Medicine and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE; ††Department of Microbiology and Molecular Genetics, University of California Irvine, School of Medicine, Irvine, CA; and ‡‡The Center for Virus Research, University of California, Irvine, Irvine, CA.
authors.forename: James V
authors.initials: JV
authors.lastname: Jester
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Morishige
authors.forename: Lbachir
authors.initials: L
authors.lastname: BenMohamed
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Brown
authors.forename: Nelson
authors.initials: N
authors.lastname: Osorio
authors.forename: Chinhui
authors.initials: C
authors.lastname: Hsiang
authors.forename: Guey Chuen
authors.initials: GC
authors.lastname: Perng
authors.forename: Clinton
authors.initials: C
authors.lastname: Jones
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wechsler
mesh_terms: D000818:Animals; D003319:Corneal Stroma / Q000473:pathology*; D004195:Disease Models, Animal; D015828:Eye Infections, Viral / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D016849:Keratitis, Herpetic / Q000473:pathology*; D018613:Microscopy, Confocal / Q000379:methods*; D011817:Rabbits; D012008:Recurrence