TRPV1 and Endocannabinoids: Emerging Molecular Signals that Modulate Mammalian Vision

Abstract

Transient Receptor Potential Vanilloid 1 (TRPV1) subunits form a polymodal cation channel responsive to capsaicin, heat, acidity and endogenous metabolites of polyunsaturated fatty acids. While originally reported to serve as a pain and heat detector in the peripheral nervous system, TRPV1 has been implicated in the modulation of blood flow and osmoregulation but also neurotransmission, postsynaptic neuronal excitability and synaptic plasticity within the central nervous system. In addition to its central role in nociception, evidence is accumulating that TRPV1 contributes to stimulus transduction and/or processing in other sensory modalities, including thermosensation, mechanotransduction and vision. For example, TRPV1, in conjunction with intrinsic cannabinoid signaling, might contribute to retinal ganglion cell (RGC) axonal transport and excitability, cytokine release from microglial cells and regulation of retinal vasculature. While excessive TRPV1 activity was proposed to induce RGC excitotoxicity, physiological TRPV1 activity might serve a neuroprotective function within the complex context of retinal endocannabinoid signaling. In this review we evaluate the current evidence for localization and function of TRPV1 channels within the mammalian retina and explore the potential interaction of this intriguing nociceptor with endogenous agonists and modulators.

Transient receptor potential cation channel, subfamilies V, member 1 (TRPV1) and M, member 1 (TRPM1) contribute to neural signaling in mouse retina.

“…These include anandamide, NADA, and hydroperoxyeicosatetraenoic acids (HpETEs). Endocannabinoid release may be associated with bright light stimulation (Ryskamp et al, 2014). This is consistent with TRPV1 activity regulating luminance dependent enhancement of spontaneous activity and maintained rates in ON GCs.…”

“…Previous publications report TRPV1 protein expression in the inner retina of rodents (Sappington et al, 2009& Leonelli et al, 2009& 2013, goldfish (Zimov &Yazulla, 2007), and non-human primates (Sappington et al, 2015). Similar to the role of TRPV1 in the PNS, the protein is thought to regulate Ca 2+ in the ganglion cell layer (GCL) and inner nuclear layer (INL) of the retina (Sappington et al, 2009(Sappington et al, & 2015Leonelli et al, 2010;Ryskamp et al, 2014). In calcium imaging studies, capsaicin, a known agonist of TRPV1, as well as TRPM1, (Shen et al, 2009) increases intracellular [Ca 2+ ] in dissociated ganglion cells (GCs; Sappington et al, 2011;Ryskamp et al, 2014).…”

“…promote prolonged neurotransmitter release from the terminals (Medvedeva et al, 2008). and in several brain regions (Gibson et al, 2008;Maione et al, 2009;Kawahara et al, 2011see Edwards, 2014& Ryskamp et al, 2014 such as the hippocampus (Gibson et al, 2008). This process shapes pain receptor sensitization in the peripheral nervous system (Medvedeva et al, 2008) and long-term potentiation for memory formation in the hippocampus (Gibson et al, 2008).…”

“…In the CNS, TRPV1 is likely gated by endovanilloids such as anandamide (Gibson et al, 2008;Maione et al, 2011;Kawahara et al, 2011;Ryskamp et al, 2014). In both LTP and LTD, TRPV1 activation by anandamide results in Ca 2+ influx, prolonged increases in intracellular [Ca 2+ ], and subsequent sustained neurotransmitter release from presynaptic terminals.…”

“…Similar to the role of TRPV1 in the PNS, the protein is thought to regulate Ca 2+ in the ganglion cell layer (GCL) and inner nuclear layer (INL) of the retina (Sappington et al, 2009(Sappington et al, & 2015Leonelli et al, 2010;Ryskamp et al, 2014). In calcium imaging studies, capsaicin, a known agonist of TRPV1, as well as TRPM1, (Shen et al, 2009) increases intracellular [Ca 2+ ] in dissociated ganglion cells (GCs; Sappington et al, 2011;Ryskamp et al, 2014). Prolonged capsaicin induced increases in intracellular [Ca 2+ ] promotes apoptosis in the inner retina (Leonelli et al, 2011;Sappington et al, 2011).…”