Abstract
The transient receptor potential vanilloid isoform 4 (TRPV4) functions as polymodal transducer of swelling, heat, stretch, and lipid metabolites, is widely expressed across sensory tissues, and has been implicated in pressure sensing in vertebrate retinas. Although TRPV4 knockout mice exhibit a variety of mechanosensory, nociceptive, and thermo- and osmoregulatory phenotypes, it is not known whether the transmission of light-induced signals in the eye is affected by the loss of TRPV4. We utilized field potentials, a measure of rod and cone signaling, to determine whether TRPV4 impacts on the generation and/or transmission of the photoreceptor light response and neurotransmission. Luminance intensity-response relationships were acquired in anesthetized wild-type and TRPV4−/− mice and evaluated for peak amplitude and implicit time under scotopic and photopic conditions. We found that the morphology of the outer retina is unaffected by the ablation of the Trpv4 gene. Calcium imaging of dissociated Müller glia showed that selective TRPV4 stimulation induces oscillatory calcium signals in adjacent rods. However, no differences in scotopic or photopic light-evoked signaling in the distal retina were observed in TRPV4-/- eyes, suggesting that TRPV4 signaling in healthy Müller cells does not modulate the transmission of light-evoked signals at rod and cone synapses.
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References
Alessandri-Haber N, Dina OA, Yeh JJ et al (2004) Transient receptor potential vanilloid 4 is essential in chemotherapy-induced neuropathic pain in the rat. J Neurosci 24:4444–4452
Barabas P, Liu A, Xing W et al (2013) Role of ELOVL4 and very long-chain polyunsaturated fatty acids in mouse models of Stargardt type 3 retinal degeneration. Proc Natl Acad Sci U S A 110:5181–5186
Brierley SM, Page AJ, Hughes PA et al (2008) Selective role for TRPV4 ion channels in visceral sensory pathways. Gastroenterology 134(7):2059–2069
Chen X, Alessandri-Haber N, Levine JD (2007) Marked attenuation of inflammatory mediator-induced C-fiber sensitization for mechanical and hypotonic stimuli in TRPV4−/− mice. Mol Pain 3:31
Duncan JL, Yang H, Doan T et al (2006) Scotopic visual signaling in the mouse retina is modulated by high-affinity plasma membrane calcium extrusion. J Neurosci 26:7201–7211
Jo AO, Ryskamp DA, Phuong TT, Verkman A, Yarishkin O, MacAulay N, Križaj D (2015) Synergistic signaling of TRPV4 and AQP4 channels is required for cell volume and calcium homeostasis regulation in retinal Müller glia. J Neurosci 35(39):13525–13537
Jo AO, Lakk M, Frye AM et al (2016) Differential volume regulation and calcium signaling in two ciliary body cell types is subserved by TRPV4 channels. Proc Natl Acad Sci U S A 113(14):3885–3890
Krizaj D (2016) Polymodal sensory integration in retinal ganglion cells. Adv Exp Med 854:693–698
Krizaj D, Ryskamp DA, Tian N et al (2014) From mechanosensitivity to inflammatory responses: new players in the pathology of glaucoma. Curr Eye Res 39:105–119
Masu M, Iwakabe H, Tagawa Y et al (1995) Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell 80(5):757–765
Mergler S, Garreis F, Sahlmüller M et al (2012) Calcium regulation by thermo- and osmosensing transient receptor potential vanilloid channels (TRPVs) in human conjunctival epithelial cells. Histochem Cell Biol. 137:743–761
Newman EA (2015) Glial cell regulation of neuronal activity and blood flow in the retina by release of gliotransmitters. Philos Trans R Soc Lond Ser B Biol Sci 370:1672
Nilius B, Voets T (2013) The puzzle of TRPV4 channelopathies. EMBO Rep. 14:152-163
Phuong TT, Yarishkin O, Križaj D (2016) Subcellular propagation of calcium waves in Müller glia does not require autocrine/paracrine purinergic signaling. Channels 10:421–427
Phuong TTT, Redmon S, Yarishkin O et al (2017) The permeability of human retinal microvascular endothelial cells is modulated by TRPV4-dependent modulation of cytoskeletal and cell-cell adhesion proteins. Journal of Physiology 595: 6869–6885
Redmon SN, Shibasaki, Krizaj D (2017) Transient receptor potential cation channel subfamily V member 4. Encyclopedia of Signaling Molecules, 2nd Edition. Sangdun Choi, Ed.
Rentería RC, Strehler EE, Copenhagen DR et al. (2005) Ontogeny of plasma membrane Ca2+ ATPase isoforms in the neural retina of the postnatal rat. Vis Neurosci. 22:263–274
Rillich K, Gentsch J, Reichenbach A et al (2009) Light stimulation evokes two different calcium responses in Müller glial cells of the guinea pig retina. Eur J Neurosci 29:1165–1176
Ryskamp DA, Witkovsky P, Barabas P et al (2011) The polymodal ion channel transient receptor potential vanilloid 4 modulates calcium flux, spiking rate, and apoptosis of mouse retinal ganglion cells. J Neurosci 31:7089–7101
Ryskamp DA, Jo AO, Frye AM et al (2014) Swelling and eicosanoid metabolites differentially gate TRPV4 channels in retinal neurons and glia. J Neurosci 34:15689–15700
Ryskamp DA, Iuso A, Krizaj D (2015) TRPV4 channels link volume regulation, calcium homeostasis and inflammatory signaling in the retina. Channels 9:70–72
Ryskamp DA, Frye AM, Phuong TT et al (2016) TRPV4 regulates calcium homeostasis, cytoskeletal remodeling, conventional outflow and intraocular pressure in the mammalian eye. Sci Rep 6:30583
Seminario-Vidal L, Okada SF, Sesma JI et al (2011) Rho signaling regulates pannexin 1-mediated ATP release from airway epithelia. J Biol Chem 286:26277–26286
Slezak M, Grosche A, Niemiec A et al (2012) Relevance of exocytotic glutamate release from retinal glia. Neuron 74:504–516
Shahidullah M, Mandal A, Delamere NA (2012) TRPV4 in porcine lens epithelium regulates hemichannel-mediated ATP release and Na-K-ATPase activity. Am J Physiol Cell Physiol. 302:C1751–C1761
Tabuchi K, Suzuki M, Minzuno A et al (2005) Hearing impairment in TRPV4 knockout mice. Neurosci Lett 382:304–308
Taylor L, Arnér K, Ghosh F (2016) Specific inhibition of TRPV4 enhances retinal ganglion cell survival in adult porcine retinal explants. Exp Eye Res 154:10–21
White JP, Cibelli M, Urban L et al (2016) TRPV4: molecular conductor of a diverse orchestra. Physiol Rev 96:911–973
Acknowledgments
This study was supported by the NIH (R01EY022076, R01EY027920, P30EY014800), the University of Utah Neuroscience Initiative, Glaucoma Research Foundation, the Willard Eccles Foundation, Glaucoma Research Foundation, the Diabetes and Metabolism Research Center at the University of Utah and unrestricted support from Research to Prevent Blindness to the Moran Eye Institute at the University of Utah.
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Yarishkin, O., Phuong, T.T., Lakk, M., Križaj, D. (2018). TRPV4 Does Not Regulate the Distal Retinal Light Response. In: Ash, J., Anderson, R., LaVail, M., Bowes Rickman, C., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1074. Springer, Cham. https://doi.org/10.1007/978-3-319-75402-4_67
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DOI: https://doi.org/10.1007/978-3-319-75402-4_67
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