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Yusuke Izuta, Imada Toshihiro, Shigeru Nakamura, Kazuo Tsubota; Intermittent Fasting prevents retinal degeneration in Rat Optic nerve and Artery Transection Model : a pivotal role of endogenous D-3-hydroxybutyrate. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):17.
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© ARVO (1962-2015); The Authors (2016-present)
The ketone body beta-hydroxybutyrate (3-HB) has been described as a calorie restriction(CR) mimetic compound, because it dramatically increases in the plasma during CR and has been demonstrated to be effective in multiple organ disorders. We previously reported at increased 3-HB play an important role of tear secretion which can be improved by CR in VDT associated dry eye.(ARVO2012) In the present study, we explored the possible role of 3-HB on the maintenance of retinal integrity by calorie restriction.
Seven-week-old male Wistar rats were used for this study. 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. This series of treatments was repeated for up to 7 days. Serum and vitreous 3-HB concentrations were measured by enzymatic method. Intraorbital optic nerve with retinal artery was transected and retinas were isolated 4 hour after transection. Retinal structural integrity was histologically analyzed and cell survival was quantified using WST assay.
Serum and vitreous 3-HB concentrations were significantly increased 18 hours after food deprivation and 0.5 hour to 1 hour after 3-HB injection. The peak 3-HB concentration of serum and lacrimal gland was approximately 15-fold compared to initial value.<br /> In the AL, retinal layer structure was disrupted 4 hours after transection, while in the IF and AL+3HB, retinal structural integrity was maintained almost the same as sham operated eye. Retinal viability (transected after 4 hours) was decreased compared with sham operated eye in the AL(35.3% ± 4.3 n=10). In contrast, decreasing of retinal viability was significantly attenuated in the IF(93.7% ± 15.5, n=4, p < 0.001) and AL+3-HB (91.6%± 5.7, n=4, p < 0.01)
Our findings suggest that increased 3-HB play an important role of protection of retina which can be improved by IF in retinal degeneration.
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