Confocal Microscopic Analysis of a Rabbit Eye Model of High-Incidence Recurrent Herpes Stromal Keratitis

James V. Jester, Naoyuki Morishige, Lbachir BenMohamed, Donald J. Brown, Nelson Osorio, Chinhui Hsiang, Guey Chuen Perng, Clinton J Jones, Steven L. Wechsler

Research output: Contribution to journalArticle

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Abstract

Purpose: 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.

Original languageEnglish (US)
Pages (from-to)81-88
Number of pages8
JournalCornea
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Keratitis
Rabbits
Incidence
Human Herpesvirus 1
Confocal Microscopy
Viruses
Trigeminal Ganglion
Viral Antigens
Stromal Cells
Infection
Cornea
Dendritic Cells
Epithelium
Epithelial Cells
Intravital Microscopy

Keywords

  • confocal microscopy
  • herpes simplex virus
  • herpes stromal keratitis
  • rabbit

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Jester, J. V., Morishige, N., BenMohamed, L., Brown, D. J., Osorio, N., Hsiang, C., ... Wechsler, S. L. (2016). Confocal Microscopic Analysis of a Rabbit Eye Model of High-Incidence Recurrent Herpes Stromal Keratitis. Cornea, 35(1), 81-88. https://doi.org/10.1097/ICO.0000000000000666

Confocal Microscopic Analysis of a Rabbit Eye Model of High-Incidence Recurrent Herpes Stromal Keratitis. / Jester, James V.; Morishige, Naoyuki; BenMohamed, Lbachir; Brown, Donald J.; Osorio, Nelson; Hsiang, Chinhui; Perng, Guey Chuen; Jones, Clinton J; Wechsler, Steven L.

In: Cornea, Vol. 35, No. 1, 01.01.2016, p. 81-88.

Research output: Contribution to journalArticle

Jester, JV, Morishige, N, BenMohamed, L, Brown, DJ, Osorio, N, Hsiang, C, Perng, GC, Jones, CJ & Wechsler, SL 2016, 'Confocal Microscopic Analysis of a Rabbit Eye Model of High-Incidence Recurrent Herpes Stromal Keratitis', Cornea, vol. 35, no. 1, pp. 81-88. https://doi.org/10.1097/ICO.0000000000000666
Jester, James V. ; Morishige, Naoyuki ; BenMohamed, Lbachir ; Brown, Donald J. ; Osorio, Nelson ; Hsiang, Chinhui ; Perng, Guey Chuen ; Jones, Clinton J ; Wechsler, Steven L. / Confocal Microscopic Analysis of a Rabbit Eye Model of High-Incidence Recurrent Herpes Stromal Keratitis. In: Cornea. 2016 ; Vol. 35, No. 1. pp. 81-88.
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