title: Activation of transient receptor potential vanilloid-1 (TRPV1) influences how retinal ganglion cell neurons respond to pressure-related stress.
abstract: Our recent studies implicate the transient receptor potential vanilloid-1 (TRPV1) channel as a mediator of retinal ganglion cell (RGC) function and survival. With elevated pressure in the eye, TRPV1 increases in RGCs, supporting enhanced excitability, while Trpv1 -/- accelerates RGC degeneration in mice. Here we find TRPV1 localized in monkey and human RGCs, similar to rodents. Expression increases in RGCs exposed to acute changes in pressure. In retinal explants, contrary to our animal studies, both Trpv1 -/- and pharmacological antagonism of the channel prevented pressure-induced RGC apoptosis, as did chelation of extracellular Ca(2+). Finally, while TRPV1 and TRPV4 co-localize in some RGC bodies and form a protein complex in the retina, expression of their mRNA is inversely related with increasing ocular pressure. We propose that TRPV1 activation by pressure-related insult in the eye initiates changes in expression that contribute to a Ca(2+)-dependent adaptive response to maintain excitatory signaling in RGCs.
authors.affiliation: a The Vanderbilt Eye Institute and Vanderbilt Brain Institute ; Vanderbilt University School of Medicine ; Nashville , TN USA.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Sappington
authors.forename: Tatiana
authors.initials: T
authors.lastname: Sidorova
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Ward
authors.forename: Rohini
authors.initials: R
authors.lastname: Chakravarthy
authors.forename: Karen W
authors.initials: KW
authors.lastname: Ho
authors.forename: David J
authors.initials: DJ
authors.lastname: Calkins
mesh_terms: D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D013312:Stress, Physiological; D050916:TRPV Cation Channels / Q000172:deficiency / Q000378:metabolism*
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse
keywords: CAP, capsaicin; EGTA, ethyleneglycol-bis(B-aminoethyl)-N, N, N1, N1-tetraacetic acid; IRTX, iodo-resinferatoxin; TRPV1; TRPV1, transient receptor potential vanilloid-1; TRPV4; TRPV4, transient receptor potential vanilloid-4; TUNEL, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling).; glaucoma; mechanosensation; neurodegeneration; optic nerve; retina; retinal ganglion cell