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Carl Weitlauf, Nicholas J. Ward, Wendi S Lambert, David J Calkins; TRPV1 Influences Dendritic Morphology of Retinal Ganglion Cells and Their Response to Elevated Pressure in the Microbead Occlusion Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2444.
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© ARVO (1962-2015); The Authors (2016-present)
Both knockout and pharmacological antagonism of the transient receptor potential vanilloid-1 (TRPV1) cation channel accelerates two-fold dysfunction and degeneration of retinal ganglion cell axons due to elevated ocular pressure via microbead occlusion of aqueous flow (Ward et al., 2014). Here we investigated whether TRPV1 knockout in mice (Trpv1 -/-) similarly accelerates ganglion cell dendritic pruning due to microbead-induced elevations in pressure.
We used microbead occlusion to elevate ocular pressure by 30-35% for 2-4 weeks in age-matched adult C57 and TRPV1 -/- mice. Retinas from both microbead- and saline-injected (control) eyes were acutely prepared as whole mounts and individual ganglion cells labeled with Lucifer yellow dye via glass microelectrodes. Following confocal imaging, we quantified dendritic field size, soma size, dendritic length, and branching for each of 138 C57 (saline N= 81, microbead N=57) and 127 Trpv1 -/- (saline N= 64, microbead N=63) ganglion cells. We also performed Sholl analysis on these cells to measure dendritic field complexity.
For C57 ganglion cells, up to 4 weeks of exposure to elevated pressure had little effect on either somatic or dendritic morphology. Ganglion cells from Trpv1 -/- retina demonstrated significantly less dendritic complexity near the cell body (60-100 um) without a change in total dendritic length; there was no difference between saline- and microbead-injected eyes within this region. Similar to C57, Trpv1 -/- did not reduce dendritic complexity at any distance from the cell body. In fact, Trpv1 -/- ganglion cells demonstrated increased Sholl complexity further from the cell body (100-300 um) with elevated pressure. This shift was more prominent for 2 weeks of elevation compared to 4 weeks.
Contrary to its effect on ganglion cell axons in the optic projection, Trpv1 -/- did not overtly accelerate loss of dendritic complexity after 2-4 weeks of elevated ocular pressure. This finding in conjunction with our C57 results are consistent with a model of progression in which axonopathy precedes dendritic pruning. That Trpv1 -/- ganglion cells from both saline- and microbead-injected eyes were less complex near the soma indicates that TRPV1 may contribute to initial branching in development.
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