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James D Lindsey, Karen X Duong-Polk, Robert N Weinreb; Altered Expression of Sirt-1, Sirt-2 and Sirt-5 Linked With RGC Protective Effect of Resveratrol Following Optic Nerve Injury.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2557.
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© ARVO (1962-2015); The Authors (2016-present)
Long term dietary supplementation with resveratrol can protect against the loss of retinal ganglion cell axons following optic nerve injury. However, it is unknown whether altered expression of sirtuins-1 (in both the cytoplasm and nucleus), -2 (predominantly in the cytoplasm), and -5 (within mitochondria) is associated with this protective effect.
C57BL/6 mice received diet supplemented with resveratrol (RD) or normal diet (ND) throughout the study (N=10 mice/diet group). After 13 months, all mice received monocular optic nerve crush (ONC). Three weeks later, the eyes were processed for paraffin section immunostaining for Sirt1, Sirt2, or Sirt5 and developed with DAB. Immunostaining intensity within the cytoplasm or nucleus of ganglion cell layer (GCL) neurons was measured using Fiji. Results for all GCL neurons in each treatment group were pooled.
Mean nuclear Sirt1 staining intensity in ND mice sham eye GCL neurons following optic nerve crush (ND-sham 29642±1717 SD, N=476 neurons; ND-crush 26676±3868, N=245; P<0.0001, Steel-Dwass-Critchlow-Fligner all pairs comparison). In contrast, nuclear Sirt1 intensity was reduced by 40% in RD-sham GCL neurons and by 31% in RD-crush GCL neurons (17915±4269, N=333 and 20388±6204, N=235, respectively; P<0.0001 in each case). The cytoplasmic Sirt1 changes were similar, though moderately smaller. Specifically, cytoplasmic Sirt1 staining intensity was reduced by 6% in the ND crush GCL neurons and by 32% and 26% in the RD sham eye neurons and crush eye neurons, respectively (ND-sham 29289±1713; ND-crush 27550±2923; RD-sham 19849±3641; RD-crush 21797±5411, respectively; N=476, 245, 333, and 235, respectively, P<0.0001 for all pairwise comparisons). Changes in cytoplasmic Sirt2 or nuclear Sirt2 differed by 10% or less. Similarly, cytoplasmic Sirt5 changes were 10% or less.
These results suggest that the protective effect of long term dietary resveratrol treatment was associated with reduction of both cytoplasmic and nuclear Sirt1 and had minimal influence on Sirt2 and Sirt5.
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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