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Yashar Seyed-Razavi, Maria J Lopez, Takefumi Yamaguchi, Pedram Hamrah; A Novel Experimental Model for Corneal Neuropathic Pain: The Ciliary Nerve Ligation Approach. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3951.
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The purpose of this study was to develop a murine model of corneal neuropathic pain.
Following a lateral canthotomy, two tractional 5-0 nylon sutures were placed temporally and the lateral conjunctival fornix incised circumferentially (90 degrees) taking care not to damage the retro-orbital venous plexus. The eye globe was rotated nasally by gently pushing the nasal conjunctival fornix with blunt tip curved forceps. A 7-0 silk suture was placed and tightened around the exposed optic nerve and surrounding ciliary nerve branches, ligating the ciliary nerves without severing them. Mice undergoing all surgical steps yet lacking the ligation suture served as sham controls. Following the procedure, two 8–0 nylon sutures for tarsorrhaphy were placed. An eye-wiping test was used to evaluate corneal sensitivity at baseline and 3, 7, and 14 days post surgery (dps) with 10μL of hyperosmolar saline solution [2M] applied to treated eyes. Light and fluorescein stained images of the ocular surface were also acquired with a slit-lamp. Excised corneal flat-mounts were stained with anti-βIII tubulin to assess nerve alterations.
No epithelial defects, corneal opacity or neovascularization were noted in either sham control or suture group. The application of hyperosmolar solution resulted in increased eye-wipe/ blink rate and behavioral changes indicative of discomfort/ pain at 3dps (31.3±5.3 vs. 13.7±1.1 wipes/ 30seconds, p=0.04), 7dps (33±4.6 vs. 16±3.5, p=0.04) and 14dps (34.3±4 vs. 16.7±3.2, p=0.03) compared to sham controls, and to baseline in wild-type un-manipulated mice (11±1.3, p<0.001, one-way ANOVA). Analysis of corneal flat-mounts revealed that ligation did not result in nerve avulsion, but did lead to a decrease in total (77±13.7 vs. 127.8±6 mm/mm2, p=0.008), subbasal (59.8±14.4 vs. 103.5±7.4, p=0.04) and stromal nerve density (17.2±1.6 vs. 27.4±2.8, p=0.04) of the central cornea at 28dps, as compared to steady state. Beading was also present along the nerve fibers following ligation.
We have developed a minimally invasive, simple and novel murine model of corneal neuropathic pain by way of ligation of ciliary nerves. This model can be applied towards understanding ocular pain, investigating the underlying mechanisms of nerve function in a neuropathic setting, as well as the therapeutic effect of drugs in the treatment of this debilitating disease.
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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