Purchase this article with an account.
Ana J Chucair-Elliott, Daniel J Carr; Dexamethasone Prevents the Loss of Corneal Nerves in Response to HSV-1 Infection. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1849.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Herpes simplex virus type 1 (HSV-1) is the leading cause of infectious corneal blindness due to chronic episodes of viral reactivation leading to herpetic stromal keratitis (HSK). Associated with the immunopathology of HSK is the development of neurotrophic keratitis, characterized by decreased or absent corneal sensation, blink reflex and tear secretion as a consequence of damage to the sensory fibers innervating the cornea. Our previous results revealed regression of the corneal nerves during the acute phase of HSV-1 infection. The aim of this study is to determine whether the loss of nerves upon HSV-1 infection is caused directly by the virus or indirectly by other means including the local immune response.
C57BL/6J mice were infected with 1,000 plaque forming units of HSV-1. At 2 h post infection (pi), mice were topically applied 0.1% dexamethasone ophthalmic solution (DEX) or artificial tears as controls onto their corneas (QID). Corneas were harvested at 2, 4, and 8 days pi and assessed for viral content by plaque assay and infiltrating myeloid-derived cells and T cells by flow cytometry. At 8 days pi corneal sensitivity was evaluated in mice using a Cochet-Bonnet esthesiometer and corneas processed for immunohistochemistry to analyze corneal nerves (β III tubulin+) via confocal imaging.
Treatment with DEX significantly preserved innervation in the cornea and corneal sensitivity at day 8 pi compared to the control-treated group. DEX treatment was also found to reduce macrophage and T cell populations but increase PMNs in the cornea in the presence of an increase in infectious virus recovered at the studied time points pi.
Our data suggest the nerve regression and loss of corneal sensitivity observed at 8 days pi correlates with infiltrating monocytes/macrophages in response to HSV-1 infection and is not a direct effect of viral replication in the cornea.
This PDF is available to Subscribers Only