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James D. Lindsey, Pinada Chindasub, Karen X. Duong-Polk, Dustin Hammond, Christopher K. Leung, Robert N. Weinreb; Differential Dendrite Retraction, Dendrite Complexity Reduction, And Protection By Brimonidine Among Various RGC Types Following Optic Nerve Crush. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4677.
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© ARVO (1962-2015); The Authors (2016-present)
To determine whether retinal ganglion cell (RGC) dendrite retraction and reduction of dendrite branching complexity following optic nerve injury varies among different RGC types, and whether brimonidine protection against these responses varies among different RGC types.
Transgenic mice expressing yellow fluorescent protein under the control of the Thy-1 promoter (Thy1-YFP mice) were imaged using a modified confocal scanning laser ophthalmoscope (mCSLO) and then received brimonidine (100 μg/kg, i.p.) or vehicle every 2 days for 30 days (N=8 mice/group). Unilateral optic nerve crush (ONC) was performed concordantly with the second treatment. Fluorescent RGCs were imaged by mCSLO twice per week. RGC cell type was assigned according to Leung et al. (IOVS 2011;52:1539). Total dendrite length was determined by filament analysis using Imaris. Dendritic branching complexity was assessed by Scholl analysis.
Type 2 RGC mean dendrite length declined to 48, 30, 8 and <1% of baseline at 4, 7, 11, 14, and 18 days after ONC in the vehicle control mice. Mean dendrite complexity declined to 45, 29, 7, 7, and 4% of baseline at 4, 7, 11, 14, and 18 days after ONC. Brimonidine treatment protected against this reduction of dendrite length and complexity. These effects were statistically significant from day 14 to day 28 after ONC where mean dendrite length in the brimonidine treated group gradually declined from 23% to 11% of mean baseline length (P<0.05 for all length and complexity measurements from days 14-28 in type 2 RGCs). Dendrite retraction and reduction of complexity were slower in type 3 RGCs than in type 2 RGCs (both P<0.01). However, brimonidine treatment had no significant effect on either mean dendrite length or dendrite complexity in type 3 RGCs at any time point (both P>0.1). Among Type 5 RGCs, the rates of dendrite retraction and complexity reduction were slower than in type 2 RGCs (both P<0.01). Unlike type 2 or type 3 RGCs, brimonidine treatment induced significant protection of type 5 RGC dendrite complexity at 3 of 4 time points in the first 2 weeks, but no significant effect at any time point after this.
Different RGC types exhibit different patterns and rates of dendrite retraction and loss of dendrite complexity after simultaneous optic nerve axon injury produced by ONC. Though brimonidine can protect against dendrite retraction and loss of dendrite complexity, the magnitude and pattern of this effect varies among different RGC types.
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