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J. G. Crowston, G. Y. Kong, I. A. Trounce, R. N. Weinreb, A. J. Vingrys, B. V. Bui; Intermittent Fasting Reverses Age-Related Vulnerability of Retinal Ganglion Cells to Pressure-Induced Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1672.
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Glaucoma prevalence increases exponentially with increasing age. The pathophysiology underlying this is not clear. Calorie restriction extends life-span and retards diseases associated with increasing age. We have recently demonstrated that aging in mice increases the vulnerability of retinal ganglion cells to acute IOP elevation. The aim of this study was to determine whether calorie restriction through intermittent fasting restores retinal ganglion cell resistance to IOP elevation in aged mice.
The functional and biochemical response to acute IOP challenge (50 mmHg for 30 minutes) was compared between old (18-month) diet restricted C57BL/6mice (alternate day fasting from 12 months, n =10) to old (18-month) and young (3 month) ad-libitum fed mice (n = 10 per group). The dark-adapted scotopic electroretinogram (ERG) was measured before, during and after IOP challenge. Statistical analysis of ERG responses (challenged/baseline %) across time was performed using ANOVA. Retina and optic nerves were further analyzed for markers of oxidative stress (HO-1) by Western blot.
Diet restricted old mice responded similarly to young mice and showed significantly less ganglion cell dysfunction during IOP challenge (p=0.009) and faster recovery (p=0.001) compared with old AL controls. One hour following IOP challenge, ganglion cell function for AL and CR mice had returned to 28±7% and 49±12% of baseline respectively. Oxidative stress in retina and optic nerve of old diet restricted mice was also significantly lower in CR mice (78 ± 21% vs 182 ± 47%, p = 0.008).
These data demonstrate that age-related vulnerability of the optic nerve to IOP-induced oxidative stress can be modified by diet manipulation.
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