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Kristin J Al-Ghoul, Robin M Voigt, Christopher B Forsyth, Ali Keshavarzian; Effects of Combined Circadian Rhythm Disruption and Alcohol on Murine Lens Structure. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3641.
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© ARVO (1962-2015); The Authors (2016-present)
It is generally accepted that cataract formation is a multifactorial process, and two factors that are associated with the development of lens opacities are alcohol abuse and circadian rhythm disruption. The present study was conducted to determine if the morphology and organization of lens fiber cells is altered after circadian rhythm disruption in conjunction with alcohol exposure.
The study utilized male C57BL/6J mice (n=58) housed in either constant light-dark (LD) 12:12 conditions or with weekly phase shifts in the LD 12:12 cycle for 3 months prior to the start of a 10-week period where the mice were fed either an alcohol-containing Nanji diet or an iso-caloric control diet, in which the alcohol calories are replaced with dextrose. Chow-fed mice were also included as a naive control group. Thus there were 5 experimental groups: 1) non-shifted, alcohol-fed, 2) non-shifted, control-fed, 3) shifted, alcohol-fed, 4) shifted, control-fed, 5) chow-fed. Animals were sacrificed at six ZT (Zeitgeber Time) points: 0, 4, 8, 12, 16, 20. Lenses were removed, then fixed, embedded, sectioned and stained for microscopic examination.
Lenses from shifted, alcohol-fed mice had structural disruptions in superficial anterior, posterior and equatorial regions. Non-shifted, alcohol-fed murine lenses were affected primarily in the anterior region, with only occasional alterations in the posterior region and no structural changes in the equatorial region. As expected, both shifted and non-shifted dextrose fed animals had disruptions of the superficial fibers and epithelium, which were consistent with ‘sugar cataracts.’ No marked structural differences were noted between ZT groups within a given treatment group. Lenses from chow-fed mice lacked the structural changes seen in the 4 experimental groups.
Animals subjected to the double-hit of circadian rhythm disruption and alcohol consumption showed the most extensive lenticular damage as compared to alcohol-only treated and naïve control animals. This indicates that circadian rhythm disruption may exacerbate the effects of alcohol on the maintenance of lens fiber structure. We speculate that systemic inflammation could be an underlying mechanism linking alcohol, circadian rhythm disruption and cataract formation.
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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