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Roy A Jacoby, Ji-Jie Pang, Samuel M Wu; Expression of TRPV4 Channels in Primate Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3249. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Transient receptor potential vanilloid 4 (TRPV4) channels are nonselective cation channels permeable to calcium, and they have been found to open in response to mechanical, osmotic, and thermal stimuli. They have been proposed to be involved in glaucoma, a blinding disease characterized by retinal ganglion cell death brought on by a poorly understood pathological mechanism. Elevation of intraocular pressure is the most noticeable risk factor for glaucoma, but how ganglion cell death is induced by intraocular pressure changes is unclear. In the mouse retina, cell swelling may elicit calcium influx and ganglion cell death via activation of TRPV4 channels, yet the expression and function of these channels in primate retina have not been studied. We studied the function and expression of pressure-sensitive TRPV4 channels in the primate retina.
TRPV4 expression and function in old world primate retinal ganglion cells were studied with specific antibodies (rabbit anti-TRPV4, 1:200, Lifespan Biosciences, Inc.), agonists (4α-phorbol 12,13-didecanoate (4α-PDD)) and antagonists (Ruthenium red) of TRPV4 channels. Ganglion cells were recorded under whole-cell voltage- and current-clamp conditions in whole mount retinas. They were superfused with Ames medium heated to approximately 35°C. Recorded cells were filled with fluorescent markers during recording and observed with a confocal microscope.
TRPV4 immunoreactivity was found in large to medium sized somas of retinal ganglion cells, as well as in the inner plexiform layer. The axons of ganglion cells and some smaller somas, presumably displaced amacrine cells, were negative for TRPV4. Under current clamp conditions, TRPV4 agonist 4α-PDD increased the firing rate of ganglion cells, which was blocked by channel blocker ruthenium red. Under voltage-clamp conditions, 4α-PDD largely enhanced EPSCs, which was completely abolished by ruthenium red.
A population of ganglion cells in the primate retina expresses TRPV4 channels. Activation of these channels can increase the spontaneous activity of some ganglion cells, making them a potential transducer of mechanical stress into increased excitability. If this activity causes chronic increased calcium levels as a result of chronic increased pressure, then it may be related to elevated intraocular pressure-induced ganglion cell death in high-tension glaucoma.
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