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Shigeru Nakamura, Ryuji Hisamura, Toshihiro Imada, Kazuo Tsubota; Intermittent fasting prevents lacrimal hypofunction in rat visual display termin user model: a pivotal role of endogenous D-3-hydroxybutyrate. Invest. Ophthalmol. Vis. Sci. 2013;54(15):917.
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© ARVO (1962-2015); The Authors (2016-present)
Calorie restriction extends life span and retards age-related chronic diseases. We previously reported that calorie restriction through intermittent fasting restores lacrimal function in VDT associated dry eye using rat model. (ARVO 2012). In this condition, serum ketone bodies concentrations increases approximately 1000 fold from the normal state. D-3-hydroxybutyrate (3-HB), a major circulating ketone body, has been demonstrated to be effective in neurological disorders such as Alzheimer’s, Parkinson’s, and found to attenuate corneal disorder in dry eye condition. In the present study, we explored the possible role of 3-HB on the attenuation of lacrimal function by calorie restriction.
8-week-old female Sprague-Dawley rats were used for this study. A series of treatments were performed under continuous exposure to low-humidity airflow (25 ± 5%, 2 - 4 m/s). Rats were placed on a swing made of a plastic pipe for 7.5 h/d, and for 16.5 hours, they were placed in individual cages without swing treatment. This series of treatments was repeated for up to 7 days. Rats were assigned to three groups: AL, ad libitum-fed animals, and IF, intermittent fasting rats, which were provided unlimited access to food every other day, AL+3-HB, 3-HB diluted with saline was injected into rat dorsal skin at a dose of 2000 mg/kg/day. Change in tear secretion was measured by the cotton thread test. Serum and lacrimal glands 3-HB concentrations were measured by enzymatic method.
A significant decrease in tear secretion was observed in the AL compared with the initial value. In the IF and AL+3-HB, slight decreases in the tear secretion were observed, although the differences were not significant compared with the initial values. Change in tear secretion was significantly suppressed in the IF (14.3 ± 0.81, n=9, p < 0.05) and AL+3-HB (13.9 ± 0.71, n=10, p < 0.05) compare to the AL day 7(10.1 ± 0.79 n=10) Serum and lacrimal glands 3-HB concentrations were significantly increased 15 hours after food deprivation and 0.5 hour to 3 hour after 3-HB injection. The peak 3-HB concentration of serum and lacrimal gland was approximately ten-fold compared to initial value.
Our findings suggest that increased 3-HB play an important role of tear secretion which can be improved by IF in VDT associated dry eye.
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