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K. Gronert, A. Sullivan, K. Lam, D. Lau, E. Zhu; Expression of Protective Lipid Circuits and Levels of Inflammatory Lipid Mediators Demonstrate Marked Gender Differences in a Mouse Model of Acute Epithelial Injury. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5526.
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Gender related prevalence of specific ocular disease such as Keratoconjunctivitis Sicca is well appreciated. Emerging evidence places early response lipid autacoids as central mediators of corneal inflammation and angiogenesis. If gender affects lipid autacoid circuits in the eye has not been determined and was the aim of the current study.
Acute self-resolving inflammation was induced in age matched male and female Balb/c mice by epithelial abrasion. Re-epithelialization was monitored by fluorescein staining and quantified by image analysis. Formation of key lipoxygenase and cyclooxygenase derived lipid autacoids in the cornea was analyzed by LC/MS/MS-based lipidomics. Resident and regenerated corneal epithelium was collected and expression of lipoxygenases, cyclooxygenases and selected receptors was analyzed by Real-Time-PCR.
Males had a faster rate of wound healing up to 48 hrs post injury compared to female mice. Lipidomic analyses demonstrated a marked increase (3-6 fold) in the basal levels and/or formation of 5-LOX, 15-LOX, 12-LOX and COX derived mediators in male mice. Expression of 15-LOX, a resident pathway that generates protective lipid autacoids, was highly upregulated (4-15 fold) in the new epithelium 7 days post corneal injury in both females and males. However, upregulation of basal epithelial 15-LOX expression was significantly lower in males.
These data add to recent evidence which implicate epithelial 15-LOX as a fundamental lipid circuit that has a key role in keratitis and wound healing. Results also provide the first evidence for gender specific activation and/or expression of lipid mediator circuits in the eye. Hence, potential gonadal steroid regulation of lipid pathways, which modulate inflammation and angiogenesis, are of considerable interest.Supported by a grant from the NEI (EY016136)
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