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James D Lindsey, Karen X Duong-Polk, Dustin Hammond, Christopher Kai-Shun Leung, Robert N Weinreb; Long Term Resveratrol Treatment Provides Differential Protection of Injured Retinal Ganglion Cell Dendrites. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2668.
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To determine whether long-term treatment with dietary resveratrol protects against retinal ganglion cell (RGC) dendrite retraction and reduction of dendrite branching complexity following optic nerve injury.
Transgenic mice expressing yellow fluorescent protein under the control of the Thy-1 promoter (Thy1-YFP mice) were fed either control diet (N=12) or the same diet supplemented with resveratrol (0.04% w/w, N=15) starting from one month of age and continuing until the end of the study 12 months later. After 11 months on these diets, fluorescent RGCs were imaged using a modified confocal scanning laser ophthalmoscope (mCSLO), then unilateral optic nerve crush was performed. Fluorescent RGCs were imaged by mCSLO weekly for the next 4 weeks. RGCs were assigned to one of six groups according to Leung et al. (IOVS 2011;52:1539). Total dendrite length and dendritic branching complexity were determined by filament analysis using Imaris. Complete loss of dendrites was assessed in Kaplan-Meier plots.
Progressive loss of dendrite length was noted in RGCs Groups 1, 2, 3, 5, and 6. Group 4 RGCs were too rarely observed for analysis. Resveratrol significantly protected against this loss at weeks 1, 2, and 4 after crush in Group 5 RGCs (P=0.002, 0.003, 0.015, respectively, t-test). Significant transient protection against this loss was observed in Group 3 RGCs (P=0.012 at week 1 after crush). Resveratrol did not significantly slow the loss in dendrite length of Group 1, 2, and 6 RGCs. Sholl analysis showed resveratrol significantly delayed loss of dendrite branching complexity in Group 3 and Group 5 RGCs at one week after crush, but not at later time points (P=0.014 and 0.013, respectively). In contrast, complete loss of dendrites was significantly delayed in RGCs Groups 1, 2, 5, and 6 (P=0.019, 0.012, 0.011, and 0.0001, respectively; log rank test).
One year treatment with dietary resveratrol significantly protected against the loss of RGC dendrites following optic nerve crush. This protective effect delayed the complete loss of dendrites in most types of RGCs as well as delayed the rate of dendrite retraction and loss of branching complexity in Group 3 and Group 5 RGCs.
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