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Nolan McGrady, Wendi S Lambert, David J Calkins; Heteromeric assembly of TRPV subunits in the retina and superior colliculus. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3537.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma, a leading cause of irreversible blindness worldwide, is associated with aging and sensitivity to intraocular pressure (IOP). Early in glaucoma, retinal ganglion cell (RGC) axon transport from the retina to superior colliculus (SC) diminishes prior to frank axonal degeneration. An RGC stress response is mediated by transient receptor potential vanilloid (TRPV) subunits, especially the TRPV1 subunit. Our work has implicated TRPV1 in transient enhancement of RGC excitability and pro-survival in glaucoma, but its association with other TRPV subunits in the retina or SC may alter is physiological contribution. Here, we investigate the expression and formation of heteromeric complexes with additional TRPV subunits in the retina and SC.
Mouse, rat, and non-human primate (NHP) retinal whole mounts were probed with TRPV2, TRPV3, TRPV5, pNF, and GFAP antibodies. TRPV subunit interactions were determined by immunoprecipitation (IP) using lysates from superior colliculus and retinas of C57 mice. Proteins were precipitated using a TRPV1 specific antibody and protein A/G magnetic beads. Western blots were performed using TRPV2, TRPV3, and TRPV5 antibodies.
In mouse and rat retinas, TRPV2 localized to RGC somas and axons while in NHP retina it localized to RGC axons. In rats, TRPV3 localized to RGC somas while TRPV3 expression was low in mouse and NHP retinas. In mice, TRPV5 localized to RGC nuclei, somas and axons; however, in rats and NHPs, low TRPV5 expression localized mainly in RGC somas. We found TRPV2, TRPV3 and TRPV5 to precipitate with TRPV1 in mouse retinal lysates. In lysates from SC, TRPV2 and TRPV3 both precipitated along with TRPV1 while TRPV5 did not.
The expression of additional TRPV subunits in the retina and their formation of complexes with TRPV1 demonstrates the diversity associated with TRPV ion-channel activity in the retina and colliculus. Additionally, how the expression profile of these subunits and heteromeric complexes are altered in response to stress might indicate how TRPV1 promotes cell-survival.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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