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James Lindsey, Karen Xuandao Duong-Polk, Dustin Hammond, Christopher Leung, Robert Weinreb; Caloric Restriction Protects Against Loss of RGC Differentiation Following Optic Nerve Injury. Invest. Ophthalmol. Vis. Sci. 2013;54(15):439.
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© ARVO (1962-2015); The Authors (2016-present)
Optic nerve injury triggers loss of retinal ganglion cell (RGC) differentiation, including loss of Thy-1 gene expression, followed by RGC death. Caloric restriction can increase lifespan, reduce markers of physiological aging, and delay the onset of certain age-related diseases. This study determined whether caloric restriction inhibits loss of Thy-1 promoter activation in RGCs following optic nerve crush.
40 transgenic mice expressing cyan fluorescent protein under control of the Thy-1 promoter were maintained on normal diet until 2 months old. Subsequently, the food was removed every other day for 24 hours from the cages of 20 of the mice until the mice were 16 months old. The control group of mice continued to receive food ad libitum. At 16 weeks of age, baseline images of fluroescent retinal neurons were collected using a blue-light confocal scanning laser ophthalmoscope and then all mice received unilateral optic nerve crush. After this, the retinas of both eyes were imaged weekly for four weeks and fluorescent spots from the same region of each retina were counted manually.
Subject survival at the end of the study was 10/20 mice (50%) in the control group and 14/20 (70%) in the caloric restriction group. The mean proportions of fluorescent retinal neurons remaining in the control group following optic nerve crush were 45±24, 35±19, 21±18, and 18±9 percent, at weeks 1 through 4, respectively. In contrast, the mean proportions of fluorescent retinal neurons remaining in the caloric restriction group were 52±17, 36±12, 27±17, and 42±23 percent at weeks 1-4, respectively (P = 0.0023 at week 4). Within the control group, the change in number of fluorescent retinal neurons between weeks 2 and 4 was > 20% less in 55% of subjects, < 20% different in 33% of subjects, and > 20% increased in 11% of subjects. Within the caloric restriction group, the change in number of fluorescent retinal neurons between weeks 2 and 4 was > 20% less in 31% of subjects, < 20% different in 31% of subjects, and > 20% increased in 38% of subjects.
The greater survival in the caloric restriction group confirms that the experimental treatment induced the lifespan enhancing effect. Because most fluorescent retinal neurons in these mice are RGCs, the imaging results indicate that caloric restriction protects against the loss of RGC differentiation following optic nerve injury.
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