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Zhijie Li, Alan Robert Burns, Rolando Rumbaut, Wayne Smith; Diet-induced obesity in mice is accompanied by reduced corneal wound healing. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5161.
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Diet-induced obesity is often accompanied by a metabolic syndrome that includes systemic inflammatory changes. While diabetic keratopathy is a well-known entity, the influence of the pre-diabetic metabolic syndrome (MS) on corneal structure and function is poorly understood.
We utilized a murine model to study the effects of a high milk fat diet (HFD) on corneal wound healing. At six-weeks of age, C57BL/6J mice were fed ad lib the HFD for an additional five weeks, then analyzed for systemic inflammatory and metabolic changes, and for alterations in the healing response to a 2 mm diameter central corneal epithelial abrasion. The HFD contained 42% (Kcal) milk fat, and control mice were fed a normal chow diet (CD).
The HFD resulted in significant increases in body weight and abdominal fat pad weights, decreases in the RER (respiratory exchange ratio) during the night-time feeding periods, moderate dyslipidemia and elevations in fasting glucose and insulin. Adipose tissue expression of CCL2 (MCP-1) and TNFα was significantly increased, and adipose tissue macrophages with increased expression of TNFα were numerous. Corneal wound closure in the CD group was complete within 24 hours, but remained open at 30 hours in the HFD group (p<0.01). Platelet accumulation in the limbus at 18 hours after wounding was reduced by 51.7% (p<0.01) in the HFD group, and CD45+ cells in the cornea were reduced by 49.1% (p<0.01) at this time. Recovery of the subbasal nerve plexus in the abraded area at 96 hours post wounding was also reduced, and there was a 32.6% (p<0.01) reduction in the density of epithelial branches.
These data indicate that diet-induced metabolic syndrome in mice is accompanied by reduced corneal wound healing and reduced immigration of leukocytes known to promote normal wound healing. Given the high incidence of metabolic syndrome in humans, associated dysregulation of healing is an important concern for sustained health of the cornea.
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