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Melissa Cooper, John W Collyer, Karen W Ho, Nicholas J Ward, David J Calkins; Age and ocular pressure influence optic nerve astrocyte remodeling during experimental glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2527.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cell axonal degeneration is influenced by complex interplay with astrocyte processes. In glaucoma, axon survival is challened by cascades dependent on aging and intraocular pressure (IOP). We aim to understand how such stressors alter cellular interactions to influence glaucomatous progression. Here we use the DBA/2J mouse model of chronic glaucoma and the inducible microbead occlusion mouse model to determine how age and elevated IOP alter astrocyte process distribution in the optic nerve.
Optic nerve cross-sections from DBA/2J mice aged 4-13 months with known IOP were analyzed for axon size, density, and astrocyte distribution using custom Matlab routines. We elevated IOP unilaterally in mice using microbead occlusion of aqueous flow and analyzed similarly. Contralateral eyes received an equivalent volume saline injection as internal control. IOP was monitored for 5 weeks using Tono-Pen XL rebound tonometry. Animals were perfused transcardially with 4% paraformaldyde. We devised a metric of astrocyte morphology ("center of mass", CoM) to define the location along nerve's radius for which 50% of the total glial area lies on either side.
For DBA/2J mice neither age (p=0.57) nor IOP (p=0.74) predicted total astrocyte coverage, which ranged from 10-50% of the cross-sectional nerve area. However, astrocyte processes distributed more evenly (determined by CoM) as coverage increased concurrent with axon loss (p<0.001). For C57 mice, the average microbead-induced IOP elevation was 30-35%. This resulted in a modest total astrocyte coverage of 15-25%. Here, increased coverage was associated with decreased CoM, indicating a bias towards the edge (p=0.02). This correlation was absent in nerves from transgenic mice missing the transient receptor potential vanilloid-1 (TRPV1) channel with the same elevation in IOP (p=0.85).
In nerves from DBA/2J mice, astrocyte process distribution is determined primarily by axonal properties rather than glaucomatous stressors directly. For C57 mice, modest IOP elevations have little influence on total astrocyte coverage of the nerve but do affect distribution. Previously, we determined that the TRPV1 cation channel contributes to astrocyte process motility after mechanical stress (Ho et al., 2014; Glia, Sept;62(9):1435-51). Consistent with this, IOP elevation had no effect on astrocyte remodeling in nerves from Trpv1 -/- mice.
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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