Retinal Cell Death Induced by TRPV1 Activation Involves NMDA Signaling and Upregulation of Nitric Oxide Synthases

  title={Retinal Cell Death Induced by TRPV1 Activation Involves NMDA Signaling and Upregulation of Nitric Oxide Synthases},
  author={Mauro Leonelli and Daniel Oliveira Martins and Luiz Roberto Giorgetti Britto},
  journal={Cellular and Molecular Neurobiology},
The activation of the transient receptor potential vanilloid type 1 channel (TRPV1) has been correlated with oxidative and nitrosative stress and cell death in the nervous system. Our previous results indicate that TRPV1 activation in the adult retina can lead to constitutive and inducible nitric oxide synthase-dependent protein nitration and apoptosis. In this report, we have investigated the potential effects of TRPV1 channel activation on nitric oxide synthase (NOS) expression and function… 

Short-Term Increases in Transient Receptor Potential Vanilloid-1 Mediate Stress-Induced Enhancement of Neuronal Excitation

The results suggest that TRPV1 may promote retinal ganglion cell survival through transient enhancement of local excitation and axonal activity in response to ocular stress.

TRPV1 and Endocannabinoids: Emerging Molecular Signals that Modulate Mammalian Vision

The current evidence for localization and function of TRPV1 channels within the mammalian retina is evaluated and the potential interaction of this intriguing nociceptor with endogenous agonists and modulators is explored.

Modulation of osmotic stress-induced TRPV1 expression rescues human iPSC-derived retinal ganglion cells through PKA

The study results indicated that the TRPV1–PKA pathway contributed to cellular response under high levels of osmolarity stress; furthermore, the PKA inhibitor had a protective effect on RGCs exposed to this stress.

Activation of the TRPV1 channel attenuates N-methyl-D-aspartic acid-induced neuronal injury in the rat retina.

Absence of Transient Receptor Potential Vanilloid-1 Accelerates Stress-Induced Axonopathy in the Optic Projection

It is proposed that TRPV1 may help neurons respond to disease-relevant stressors by enhancing activity necessary for axonal signaling in response to elevated ocular pressure.

Enhanced Vascular PI3K/Akt-NOX Signaling Underlies the Peripheral NMDAR-mediated Pressor Response in Conscious Rats

Findings implicate vascular PI3K/Akt-protein kinase C signaling in the peripheral NMDAR-mediated increases in vascular NO and NOX activation (ROS), which ultimately lead to calcium influx and pressor response in conscious rats.

Transient Receptor Potential Melastatin-3 (TRPM3) Mediates Nociceptive-Like Responses in Hydra vulgaris

The results demonstrate the presence of conserved molecular oxidative/nociceptive-like pathways at the primordial level of the animal kingdom and in the freshwater coelenterate Hydra vulgaris, the most primitive organism possessing a nervous system.

Studying Nitric Oxide in the Developing Retina: Neuromodulatory Functionsand Signaling Mechanisms

It is concluded that NO is a major atypical neurotransmitter in the retina, regulating signaling events associated with the development of embryonic retinal neurons and glial cells.

The modulatory effect of anandamide on nitroglycerin-induced sensitization in the trigeminal system of the rat

The results show that NTG is able to increase TRPV1, nNOS, NF-κB and COX-2 and decrease KAT-II expression in the C1–C2 segments, and AEA modulates the NTG-induced changes, thus it influences the activation and central sensitization process in the trigeminal system, probably via CBs.



TRPV1 stimulation triggers apoptotic cell death of rat cortical neurons.

TRPV1 receptors modulate retinal development

TRPV1 receptors are involved in protein nitration and Müller cell reaction in the acutely axotomized rat retina.

Nitric Oxide Synthase Inhibition Delays Axonal Degeneration and Promotes the Survival of Axotomized Retinal Ganglion Cells

It is concluded that NO synthesized by retinal iNOS and cNOS plays a major role in RGC death and retrograde axonal degeneration following axotomy.

TRPV1: contribution to retinal ganglion cell apoptosis and increased intracellular Ca2+ with exposure to hydrostatic pressure.

RGC apoptosis induced by elevated hydrostatic pressure arises substantially through TRPV1, likely through the influx of extracellular Ca(2+).

Transient Receptor Potential Vanilloid Subtype 1 Mediates Microglial Cell Death In Vivo and In Vitro via Ca2+-Mediated Mitochondrial Damage and Cytochrome c Release1

This study is the first to demonstrate that microglia express TRPV1, and that activation of this receptor may contribute to microglial damage via Ca2+ signaling and mitochondrial disruption.

Contributions of TRPV1, endovanilloids, and endoplasmic reticulum stress in lung cell death in vitro and lung injury.

Testing the hypothesis that endovanilloids produced following lipopolysaccharide (LPS) treatment activate TRPV1 and cause endoplasmic reticulum stress/GADD153 expression in lung cells, representing a mechanistic component of lung injury demonstrates that ER stress and cytotoxicity are not essential for pulmonary edema.

Direct imaging of NMDA-stimulated nitric oxide production in the retina

D diaminofluorescein-2 (DAF-2) is used to image real-time NO production in turtle retina in response to stimulation with N-methyl-D-aspartate (NMDA) and suggests that NO signal transduction may be more selective than suggested, and that NO may play significant intracellular roles in cells that produce it.

Importance of the non-selective cation channel TRPV1 for microglial reactive oxygen species generation

Transient Receptor Potential Vanilloid 1 Agonists Cause Endoplasmic Reticulum Stress and Cell Death in Human Lung Cells

It is concluded that activation of ER-bound TRPV1 and stimulation of GADD153 expression via the EIF2 αK3/EIF2α pathway represents a common mechanism for cytotoxicity by cell-permeable TRpV1 agonists.