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S. B. Wang, K. Gronert; Resident Protective Lipid Circuits Exhibit Sex-Specific Differences in Reparative Inflammatory Responses Triggered by Recurrent Epithelial Injury. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1565.
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© ARVO (1962-2015); The Authors (2016-present)
Sex has long been recognized as a risk factor in many inflammatory/immune diseases such as Dry Eye, a disease prevalent in post-menopausal women that often results in recurrent corneal epithelial injury. Resident lipid circuits (15-LOX, LXA4) in the cornea have emerged as critical mediators of inflammatory resolution and angiogenesis. More importantly, sex-specific differences in these lipid pathways remain unknown especially in the eye. To this end, we examined if sex differentially regulates these circuits.
A model of recurrent epithelial injury was induced in age-matched male and female Balb/c mice by re-abrading corneas 7 days post epithelial abrasion. Re-epithelialization was monitored by fluorescein staining and quantified by image analysis. Neovascularization was quantified via immunofluoresence using CD31 as an endothelial marker. Myeloperoxidase activity was used as a marker for PMN infiltration. PMN and macrophage infiltration were visualized via immunofluoresence in 5µm frozen sections using GR-1 and F4/80, respectively. Expression of select inflammatory and angiogenic mediators was measured using real-time PCR. Mouse eyes were treated with 17ß-estradiol (E2) (1 ng topically t.i.d.) or saline alone for 9 days.
48 hours post reinjury, females displayed a significant delay in wound healing compared to males, which correlated with a marked increase in PMN infiltration (1.4 fold) and lower expression of 15-LOX. Treatment with E2 markedly regulated the expression of protective lipid circuits in the corneal epithelium. Reinjury amplified corneal inflammation and triggered neovascularization in both sexes. However, the angiogenic response was notably amplified in males compared to females (53%).
These data provide evidence for selective sex-specific differences in inflammatory, reparative and angiogenic responses in the cornea. More importantly, they provide the first evidence for sex-specific regulation of protective lipid circuits. Given the sex-related prevalence of prominent ocular diseases, sex steroid regulation of protective lipid circuits clearly warrants further investigation.
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