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Neal Mecum, Tori Denis, Will Bushey, Ian D Meng; Lacrimal Gland Excision in Male and Female C57BL/6 Mice Causes Pain- and Anxiety-like Behavior. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2241. doi: https://doi.org/.
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Previously, we have shown that female mice exhibit a more severe dry eye phenotype following lacrimal gland excision (LGE) induced dry eye, as evidenced by increased fluorescein scores and cornea epithelial apoptosis. Signs of ocular discomfort and pain are the most common symptoms of dry eye disease. The aim of the present study was to determine whether sex differences are also observed following LGE using specific assays to assess pain and anxiety-like behaviors.
Male and female C57BL/6 mice were obtained from Jackson Labs. Under isoflurane, a unilateral LGE was performed, excising either the left extraorbital gland, or both the extraorbital and intraorbital glands. For SHAM surgeries, incisions were made to partially expose both the extra- and intraorbital glands. Eye closure (squinting) was measured using a ratio consisting of the height of the gap between the upper and lower eyelids and the distance separating the two canthi. The topical anesthetic tetracaine (0.5% in ophthalmic solution) or vehicle was applied to the cornea 5 minutes prior to measuring eye closure. Sensitivity to cold was examined by counting the total number of swipes following the application of acetone (15ul) to the forehead. To assess anxiety and pain-suppressed behaviors, locomotor activity and rearing behavior was measured in open field chambers.
Following double LGE, both male and female mice exhibited squinting in the ipsilateral eye, signified by a significant decrease in the eye closure ratio. Single LGE caused significant decrease in the eye closure ratio only in female mice. Topical application of tetracaine, rescued eye closure ratios to normal SHAM eye closure levels. Evaporative cooling produced by the application of acetone to the forehead caused a significant increase in swiping behavior in both male and female animals after single and double LGE when compared to SHAM. In the open field test, double LGE significantly decreased the total distance traveled, number of vertical rears, and vertical rearing time for both sexes. Single LGE reduced the number of vertical rears and vertical rearing time only in female mice.
These results indicate that single LGE produces greater irritation and pain in female mice. Pain and anxiety-like behaviors in dry eye provide important preclinical endpoints that can be utilized when investigating the value of potential therapeutic interventions.
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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