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Members of the transient receptor potential (TRP) family of cation-selective ion channels are candidates for mediating stress signals, since different subunits transduce a variety of stimuli relevant in both normal and pathogenic physiology. We addressed this possibility for the TRP vanilloid-1 (TRPV1) subunit by comparing how the optic projection of<jats:italic>Trpv1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice and age-matched C57 controls responds to stress from elevated ocular pressure, the critical stressor in the most common optic neuropathy, glaucoma. Over a 5 week period of elevated pressure induced by microbead occlusion of ocular fluid,<jats:italic>Trpv1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>accelerated both degradation of axonal transport from retinal ganglion cells to the superior colliculus and degeneration of the axons themselves in the optic nerve. Ganglion cell body loss, which is normally later in progression, occurred in nasal sectors of<jats:italic>Trpv1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>but not C57 retina. Pharmacological antagonism of TRPV1 in rats similarly accelerated ganglion cell axonopathy. Elevated ocular pressure resulted in differences in spontaneous firing rate and action potential threshold current in<jats:italic>Trpv1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>ganglion cells compared with C57. In the absence of elevated pressure, ganglion cells in the two strains had similar firing patterns. Based on these data, we propose that TRPV1 may help neurons respond to disease-relevant stressors by enhancing activity necessary for axonal signaling.<\/jats:p>","DOI":"10.1523\/jneurosci.4089-13.2014","type":"journal-article","created":{"date-parts":[[2014,2,26]],"date-time":"2014-02-26T17:23:41Z","timestamp":1393435421000},"page":"3161-3170","source":"Crossref","is-referenced-by-count":81,"title":["Absence of Transient Receptor Potential Vanilloid-1 Accelerates Stress-Induced Axonopathy in the Optic Projection"],"prefix":"10.1523","volume":"34","author":[{"given":"Nicholas J.","family":"Ward","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen W.","family":"Ho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendi 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