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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)
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.
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.
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.
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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