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Sue Aicher, Clayton Hudson, Sam Hermes, Deborah Hegarty; Neuropathic changes in corneal nerve fibers after abrasion injury. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1288.
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© 2017 Association for Research in Vision and Ophthalmology.
Alterations in ocular sensation occur in patients with dry eye disease as well as those who have undergone vision correction surgery. Pain experienced by these patients may indicate a neuropathic pain condition. We tested the hypothesis that neuropathic changes in corneal nerve fibers underlie changes in ocular sensation using a corneal abrasion injury in rats. These basic science studies will determine the relationship between changes in corneal fiber density and neurochemical content and ocular sensation after a corneal injury.
A unilateral central corneal injury was made using topical application of heptanol in male Sprague-Dawley rats. At time points after corneal abrasion injury, stereotypic nociceptive eye wipe responses to ocular application of noxious menthol were measured in either the abraded eye or the non-abraded control eye. At the conclusion of behavioral testing, rats were euthanized and perfused with aldehydes. The corneas were removed and processed for immunohistochemistry for beta-tubulin and nociceptive molecular markers. Corneal fibers were visualized with confocal microscopy and analyzed using Imaris software. T-tests were used for statistical analyses.
Rats tested in the injured eye 24 hours after abrasion had a significantly higher average number of eye wipe responses to ocular application of noxious menthol (13.8 ± 0.8 (SEM) eye wipes; n=4) as compared to rats tested on the uninjured side (7.7 ± 0.9 (SEM) eye wipes; n=3; t-test, p=0.002). Paradoxically, abraded corneas from the 24 hour time point had dramatically reduced corneal fiber density. One week post-injury, rats tested on the injured side (9.3 ± 0.5 (SEM) eye wipes; n=4) did not show any significant differences from rats tested on the uninjured side (9.0 ± 2.3 (SEM) eye wipes, n=4). While corneal fiber density showed evidence of recovery at one week, it was reduced compared to uninjured corneas.
Abrasion injury reduces corneal fiber density; however this reduction does not appear to be directly correlated to behavioral responses to noxious corneal stimulation. We believe that the neurochemical content of corneal fibers will be a better predictor of pain sensitivity at the corneal surface than overall density. These findings will provide insights into the dynamics of pain transmission in the cornea and will deepen our understanding of the neuropathic changes that occur in corneal nerve fibers after injury.
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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