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Aubrey Hargrave, Madhavi Chintalapati, Pooja Mehta, Paul Landry, Sri Magadi, Clifton Wayne Smith, Alan Robert Burns; Reversibility of diet-induced corneal degeneration in a mouse model. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© 2017 Association for Research in Vision and Ophthalmology.
In a mouse model of metabolic syndrome, prior to the development of hyperglycemia, 10 weeks on a high fat diet (HFD) causes a decline in central corneal nerve density (Hargrave A et al., IOVS 2015; 56(7):3076). The current study extends this observation and evaluates early and long-term morphological and functional corneal changes caused by a HFD, and determines if these changes can be reversed after resuming a normal diet.
Five week old male C57BL/6 mice (n=95) were fed a HFD (42% Kcal milk fat) for 1, 5, 10, and 15 weeks. Age-matched mice on a normal chow diet served as controls. Diet reversal mice were fed a HFD for 5 weeks followed by a normal diet for 5 or 10 weeks. Corneal sensitivity was measured using a Cochet-Bonnet aesthesiometer. Excised corneas were stained with anti-tubulin β III antibody. Nerve density was analyzed using immunofluorescence microscopy with a custom MATLAB program and stereology. Epithelial thickness was determined using plastic embedded 0.5 μm thick transverse sections. Data were analyzed using a two-tailed unpaired t-test or a one-way ANOVA with a Tukey post-test. A p-value ≤ 0.05 was considered significant.
As expected, epithelial thickness and nerve density decreased with age in normal chow fed mice; however, the onset and rate of this decline was accelerated in mice on a HFD. Compared to age-matched chow fed mice, 1 week on a HFD reduced corneal sensitivity by two-fold (p=0.027) and the epithelium was 16% thinner after 10 weeks on a HFD (p=0.003). After 15 weeks on a HFD, nerve sensitivity decreased further (3.5-fold; p<0.0001) and this was mirrored by a 25% decrease in vertical nerve branches (p=0.004). Remarkably, diet reversal for 5 weeks restored epithelial thickness while diet reversal for 10 weeks restored nerve sensitivity and density.
Mice on a HFD show an accelerated decline in corneal sensitivity, nerve density and epithelial thickness. These effects are largely reversed when the mice resume a normal diet, a testimony to the plasticity and regenerative capacity of the cornea.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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