Abstract
Lacrimal gland excision (LGE) induced dry eye produces more severe corneal damage in female mice, yet signs of LGE-induced ocular pain and anxiety in male and female mice have not been characterized. Excision of either the extraorbital gland (single LGE), or both the extraorbital and intraorbital glands (double LGE) was performed in male and female C57BL/6J mice to induce moderate and severe dry eye. Ongoing pain was assessed by quantifying palpebral opening and evoked nociceptive responses after corneal application of capsaicin and menthol. The open-field and plus maze were used to assess anxiety. Single LGE caused a reduction in palpebral opening and an increase in capsaicin and menthol-evoked responses only in female mice. Furthermore, single LGE produced signs of increased anxiety in female but not male mice. Overall, female mice appear more susceptible to signs of ocular pain, irritation, and anxiety in response to aqueous tear deficiency.
Highlights
Lacrimal gland excision (LGE) induced dry eye produces more severe corneal damage in female mice, yet signs of LGE-induced ocular pain and anxiety in male and female mice have not been characterized
LGE-induced plasticity in corneal afferents includes an increase in co-expression of TRPM8 and TRPV1, which is matched by a greater proportion of cold responsive corneal afferents that are activated by noxious heat after L GE18
Post hoc analysis revealed a difference between female and male mice after single LGE (0.657 ± 0.036 versus 0.801 ± 0.011, p < 0.001, Fig. 1B), whereas double LGE produced a comparable reduction in palpebral opening in both female and male mice (0.556 ± 0.03 and 0.552 ± 0.024, respectively, Fig. 1B)
Summary
Lacrimal gland excision (LGE) induced dry eye produces more severe corneal damage in female mice, yet signs of LGE-induced ocular pain and anxiety in male and female mice have not been characterized. A recent comparison of female and male rats found that LGE resulted in greater signs of corneal damage and produced a greater increase in blink rates in female rats[13] Consistent with these results, a significant sex difference has been reported in the inflammatory response to LGE in male and female mice. Despite producing a comparable reduction in tear volume in male and female mice, LGE caused greater immune cell infiltration and corneal epithelial cell apoptosis in female compared to male m ice[10] These results are consistent with epidemiological reports that DED is more prevalent in women compared to m en[19,20,21,22]
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