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Yusuke Izuta, Imada Toshihiro, Ryuji Hisamura, Shigeru Nakamura, Kazuo Tsubota; Calorie restriction protects against retinal degeneration in acute glaucoma model through altering the metabolic profile.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2564.
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© 2017 Association for Research in Vision and Ophthalmology.
Calorie restriction (CR) has been reported that provides the various benefits for health. We previously reported that CR prevent the retinal degeneration in rat glaucoma model, and increased exogenous 3-Hydroxybutyrate (3HB) during CR play a role in protective effect (ARVO2015). In this study, to clarify the mechanisms of the neuroprotective effect by 3HB, we compared the changes in metabolic profile of CR and exogenously applied 3HB.
Seven-week-old male wistar rats were used for this study. Rats were assigned to three groups: every other day fasting (CR), 2000 mg/kg/day 3HB subcutaneous injection (3HB), and ad libitum feeding (AL). Seven days after treatment, the retinal degeneration was caused by optic nerve and central retinal vessels (ONV) transection in one eye. Another eye was served as sham operation. Metabolome analysis, quantifying total 205 kinds of metabolites by capillary electrophoresis-mass spectrometry, was performed in the retina from 1 hour after the transaction in each treatment. Retinal cell degeneration rate was confirmed using WST assay. Clustered Heat map by using Z score was constructed by R software (http://www.r-project.org/).
In cell survival rate after the ONV transection, CR group (81.7% ± 30.9, p < 0.001) and 3HB group (77.3% ± 26.7, p < 0.01) showed significantly higher value than AL group (34.2% ± 14.4). Various metabolites were changed after the ONV transection in each treatment. A series of intermediates in pentose phosphate pathway (PPP): G6P, 6-phosphogluconate, PRPP, and NADPH were preserved in CR and 3HB groups, not in AL group, as same level as those of the normal retina.
Enhancement of PPP has been reported to be involved in neuroprotection. Our finding suggest that activation of PPP via increased level of 3-HB is potent mechanism underlines in beneficial effect of CR in retinal degeneration.
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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