September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
IL-6 Contributes to Corneal Nerve Degeneration Following HSV-1 Infection
Author Affiliations & Notes
  • Ana J Chucair-Elliott
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Daniel J Carr
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Footnotes
    Commercial Relationships   Ana Chucair-Elliott, None; Daniel Carr, None
  • Footnotes
    Support  National Institutes of Health (NIH) grant: R01 EY021238, Oklahoma Center for Adult Stem Cell Research (OCASCR) grant through the Oklahoma Tobacco Settlement Endowment Trust, and an unrestricted grant from Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 317. doi:
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    • Get Citation

      Ana J Chucair-Elliott, Daniel J Carr; IL-6 Contributes to Corneal Nerve Degeneration Following HSV-1 Infection. Invest. Ophthalmol. Vis. Sci. 2016;57(12):317.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Herpes simplex virus type I (HSV-1) is a leading cause of neurotrophic keratitis, characterized by decreased or absent corneal sensation and blink reflex 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 is caused directly by the virus or indirectly by the elicited immune response.

Methods : C57BL/6J mice were infected with 103 plaque forming units of HSV-1. At 2 h pi, mice were topically applied 0.1% dexamethasone ophthalmic solution (DEX) or artificial tears as controls (VEH) onto their corneas (4 times/day). Corneas were harvested at 2, 4, and 8 days post-infection (pi) and assessed for viral content by the plaque assay and infiltrating myeloid cells and T cells by flow cytometry. Corneal sensitivity was evaluated in mice using a Cochet-Bonnet esthesiometer and corneas were processed for immunohistochemistry (IHC) to analyze corneal nerves (β III tubulin). The corneal content of chemokines and inflammatory cytokines was assayed by suspension array. In other experiments, IL-6 neutralizing antibody or isotype control was administered subconjuctivally to infected mice and corneas from both groups were subjected to sensitivity measurements and analysis of nerves, viral content, and infiltrating inflammatory cells.

Results : DEX significantly preserved both the area occupied by nerves in the cornea and corneal sensitivity upon infection. DEX reduced both myeloid and T cell populations in the cornea and resulted in unchanged viral content at 4 and 8 days pi. Chemokine and inflammatory cytokine levels were greatly increased in infected corneas treated with VEH at 8 days pi but suppressed by DEX. Neutralization of IL-6 without changes in other cytokine levels resulted in partial preservation of corneal sensitivity and nerves even in the presence of an increased viral load.

Conclusions : Our data suggest the nerve regression is caused by the elicited immune response to HSV-1 rather than by the direct effect of viral replication in the cornea. Treatment of infected corneas with DEX results in anatomical and functional preservation of corneal nerves. Studies using neutralizing antibodies support a role of IL-6 as one of the mediators of corneal nerve damage following infection with HSV-1.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.


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