June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Dietary DHA Abrogate Intrinsic Sex-Specific Differences in Lacrimal Gland Lipid Mediator Circuits during Dry Eye
Author Affiliations & Notes
  • Kyle Hu
    Vision Science, University of California Berkeley, Berkeley, CA
  • Samantha Wang
    Vision Science, University of California Berkeley, Berkeley, CA
  • Erick Lu
    Vision Science, University of California Berkeley, Berkeley, CA
  • Patrick Salveson
    Vision Science, University of California Berkeley, Berkeley, CA
  • Yuan Gao
    Vision Science, University of California Berkeley, Berkeley, CA
  • Karsten Gronert
    Vision Science, University of California Berkeley, Berkeley, CA
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4344. doi:
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    • Get Citation

      Kyle Hu, Samantha Wang, Erick Lu, Patrick Salveson, Yuan Gao, Karsten Gronert; Dietary DHA Abrogate Intrinsic Sex-Specific Differences in Lacrimal Gland Lipid Mediator Circuits during Dry Eye. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4344.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: We previously demonstrated sex-specific differences in corneal inflammatory reparative responses, which are mediated by estrogen modulation of protective lipid mediators derived from dietary polyunsaturated fatty acids (PUFA). Sex-steroids have long been implicated in Dry Eye (DE) due to the prevalence of disease incidence in women. Sjogren’s Syndrome causes DE by dysregulating immune responses in the lacrimal gland. A post hoc clinical study found a correlation between dietary ω-3 PUFA in women and decreased incidence of DE symptoms. ω-3 DHA is of interest to immune regulation as it’s metabolized into potent lipid mediators. We investigated whether lipid mediator pathways are present and functional in the lacrimal gland, if they exhibit sex-specific differences, and if a DHA-rich diet can confer protective actions against DE development

Methods: DE was induced using a model of desiccating stress and scopolamine. Mice were placed on a DHA-rich or DHA-deficient diet for 4 weeks before DE induction. Schirmer’s test was used to assess tear levels. PMN levels were quantified using myeloperoxidase assay, lipid mediator formation by LC/MS/MS-based lipidomics, and gene expression via QPCR. Leukocyte populations were assessed by IHC

Results: Lacrimal glands highly express inflammatory lipid circuits (COX, 15-LOX), which are regulated by desiccating stress. Female mice exhibited an amplified inflammatory response compared to males, evidenced by a marked early infiltration of PMNs, increased pro-inflammatory PGE2, and decreased pro-resolving LXA4. Mice that received the DHA-rich diet had higher tear production (0.9mm) compared to their DHA-poor diet counterparts (0.3mm), suggesting greater protection against desiccating stress. DHA-rich mice contained greater levels of DHA and EPA, and lower levels of ω-6 PUFA AA. Levels of PGE2 were downregulated 2.4-fold and pro-resolving lipid mediators were upregulated in mice on the enriched DHA diet

Conclusions: These results provide the first evidence that lipid autacoid circuits are expressed and functional in vivo in lacrimal glands. There is a sex-specific difference in the inflammatory response to desiccating stress. Dietary DHA in females shifts levels of lipid mediators to resemble males and may confer protection against disease progression by downregulating the immune regulatory COX/PGE2 pathway, a primary target of corticosteroids and NSAIDs

Keywords: 486 cornea: tears/tear film/dry eye • 506 eicosanoids • 576 lacrimal gland  
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