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Di Wu, Yuan Gao, Matthew Greenwood, Tran Bianconi, Karsten Gronert; Expression of Pro-resolving Lipid Mediator Circuits in Eyelid and Conjunctiva and Sex-specific Responses to Immune-driven Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):299.
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© ARVO (1962-2015); The Authors (2016-present)
Dry Eye is a common inflammatory and autoimmune ocular surface disease. Even though immune driven Dry Eye pathogenesis has been studied in the cornea, lacrimal gland and conjunctiva, the eyelid has largely been ignored. Our previous study provides strong evidence that the specialized pro-resolving lipid mediators (SPM) and PMN have striking and sex-specific regulatory roles in Dry Eye disease. In the present study, we investigated if SPM circuits are expressed and functional in the eyelid and conjunctiva and exhibit sex-specific differences in Dry Eye.
Matched male and female C57/BI mice of both sexes were subjected to the standard model of immune driven Dry Eye disease. Whole eyelids and palpebral and bulbar conjunctiva were harvested. Lipid mediators were identified and quantified by LC/MS/MS-based lipidomics. PMN were quantified by myeloperoxidase assay, and mRNA expression quantified by QPCR. Goblet cell density was measured by image-analysis and visualized by periodic-Schiff reagent.
Healthy control male and female mice had a significant expression and activity of SPM circuits in eyelids and conjunctiva. The tissue levels of DHA, 17-HDHA and LXA4 were significantly higher in the eyelids of female compared to male mice (P<0.0232). Dry Eye induced significant reduction in SPM circuit activity in the eyelid that correlated with reduced goblet cell density, and a marked increase in COX-2 expression in both female and male mice. Sex-specific dry eye pathogenesis was evident in both the eyelid and conjunctiva. After inducing desiccating stress, males had strikingly higher tissue levels of the immune regulatory SPM, LXA4, when directly compared to females.
This study provides the first evidence that SPM circuits are expressed and functional in eyelids and conjunctiva. Desiccating stress activates SPM circuits and causes pathological changes in the whole eyelid that are distinct from the conjunctiva. The results also identify for the first time sex-specific difference in the immune response triggered by desiccating stress in eyelids and conjunctiva.
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