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Zhijie Li, Aubrey Hargrave, Yunxia Xue, Samuel D Hanlon, Alan Robert Burns, Clifton Wayne Smith; Short-term high fat diet feeding reduces corneal wound healing in mice.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):847.
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© ARVO (1962-2015); The Authors (2016-present)
Obesity is a serious public health problem. 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 short term high milk fat diet (HFD) on the cornea, and on the cornea’s ability to heal surface wounds.
Six-week old C57BL/6J mice were maintained under a 12-h light/12-h dark (LD) cycle and fed ad lib the HFD (42% milk fat) for 10 days (a condition that did not alter fasting glucose levels). Control mice were fed a normal chow diet (CD). Some mice were analyzed for neutrophil influx in the corneal limbus and corneal expression of the circadian clock gene Rev-erbα (data collected at 3 h intervals over a 24 h cycle). Corneal sensitivity to touch was measured using the Cochet-Bonnet aesthesiometer. Other mice were given 2mm diameter corneal epithelial abrasions and analyzed for re-epithelialization, mitosis, leukocyte and platelet influx, recovery of subbasal nerve plexus density and corneal sensitivity to touch.
Corneas from mice on the CD exhibited significant flux in tissue neutrophils in the limbus (peaking at zeitegeber time (ZT) 18 and nadir at ZT2), and expression of Rev-erbα (peak, ZT11; nadir, ZT20). Mice on the HFD failed to exhibit these fluxes, and as previously reported, (Hargrave et al., IOVS 2016; 57(12)) corneal sensitivity was significantly reduced (p<0.05), though nerve density was not reduced by the HFD. 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) and epithelial cell division was significantly reduced (p<0.01). Neutrophil and γδT cell migration to the wound area, and platelet accumulation in the limbus at 18 hours after wounding were reduced by 80%, 25% and 40% respectively (p<0.01) in the HFD group. Recovery of the subbasal nerve plexus density and nerve sensitivity were also reduced (56% and 50%, respectively, p<0.01).
These data indicate that a short-term HFD, prior to inducing changes in fasting blood glucose levels, alters circadian rhythms in the cornea as has been reported in other tissues, alters nerve sensitivity in the cornea, and significantly reduces key parameters of corneal wound healing.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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