June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Attenuating Ocular Sulfur Mustard Injury with Restasis
Author Affiliations & Notes
  • Marion K Gordon
    Pharmacology & Toxicology, Rutgers University, Piscataway, New Jersey, United States
  • Rita A Hahn
    Pharmacology & Toxicology, Rutgers University, Piscataway, New Jersey, United States
  • Peihong Zhou
    Pharmacology & Toxicology, Rutgers University, Piscataway, New Jersey, United States
  • Yokechen Chang
    Pharmacology & Toxicology, Rutgers University, Piscataway, New Jersey, United States
  • Kathy K H Svoboda
    Biomedical Sciences, Baylor College of Dentistry, Texas A&M, Dallas, Texas, United States
  • Donald Gerecke
    Pharmacology & Toxicology, Rutgers University, Piscataway, New Jersey, United States
  • Footnotes
    Commercial Relationships   Marion Gordon, None; Rita Hahn, None; Peihong Zhou, None; Yokechen Chang, None; Kathy Svoboda, None; Donald Gerecke, None
  • Footnotes
    Support  NIAMS U54 AR055073
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 170. doi:
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    • Get Citation

      Marion K Gordon, Rita A Hahn, Peihong Zhou, Yokechen Chang, Kathy K H Svoboda, Donald Gerecke; Attenuating Ocular Sulfur Mustard Injury with Restasis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):170.

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

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Abstract

Purpose : Sulfur mustard (SM) exposure to the eye causes injury via initiating an inflammatory response and inducing matrix metalloproteinases. In the cornea, epithelial-stromal separation results. Our goal was to determine whether the immunosuppressive action of Restasis would promote wound healing of SM-exposed eyes.

Methods : The right eyes of 6 New Zealand white rabbits were exposed to 0.4 uL neat SM for 2 hr. Eye injury was followed at 1, 3, 7, 14, 16, 21 and 28 days post exposure via photography and pachymetry. Right eyes of 6 other rabbits were also exposed to 0.4 uL SM, but these received a drop of Restasis after the 2 hr exposure, and a second drop 12 hr later. Restasis treatment was continued twice per day throughout the 28 day study. Three unexposed rabbits served as Restasis alone controls.

Results : At 1, 3, 7 and 14 days post exposure the SM-exposed right eyes were cloudy and irritated in animals exposed to SM and also in those receiving Restasis after SM. At 14 and 16 day after exposure some improvement was observed, but corneal cloudiness was still apparent in both the groups. At 21and 28 days post exposure, corneal clarity had improved in both groups, but was still not yet optimal. However, signs of improvement were derived from the fact that, after 28 days, when RNA was extracted from dissected corneas, qPCR showed that the mRNA level of IL1alpha was 42% lower, the Cox 2 mRNA level was 31% lower, and the MMP-9 mRNA level was 57% lower in the corneas receiving 28 days of Restasis treatment after SM exposure, as compared to those exposed to SM without subsequent therapy.

Conclusions : Ocular SM exposure induces inflammation and matrix metalloproteinase activity. Restasis treatment after SM exposure was found at 28 days post exposure to have reduced inflammatory markers and MMP-9 mRNA levels. However, Restasis did not fully promote repair of SM injury, as many corneas were still cloudy. Future work will test whether a combination therapy should be used targeting the inflammation with Restasis and the matrix metalloproteinase activity with doxycycline.
Supported by NIAMS U54AR055073

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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