The P2X7 receptor in retinal ganglion cells: A neuronal model of pressure-induced damage and protection by a shifting purinergic balance

Mitchell, Claire H.; Lu, Wennan; Hu, Huiling; Zhang, Xiulan; Reigada, David; Zhang, Mei

doi:10.1007/s11302-009-9142-6

Cited by 45 publications

(22 citation statements)

References 53 publications

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“…Adenosine acting at adenosine A 3 receptors inhibits the P2X 7 -induced increases in calcium and apoptosis of retinal ganglion cells, suggesting that the balance between the extracellular ATP and adenosine levels determines the level of the ganglion cell death, and that dephosphorylation of extracellular ATP into adenosine might have neuroprotective effects (Zhang et al, 2006a,b;Mitchell et al, 2009;Hu et al, 2010). The rapid release of endogenous adenosine is an important component of the retinal response to ischemiaehypoxia Ribelayga and Mangel, 2005).…”

Section: Protection From Neuronal Degeneration By Adenosinementioning

confidence: 99%

Purinergic signaling in retinal degeneration and regeneration

Reichenbach

Bringmann

2016

Neuropharmacology

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Section: Protection From Neuronal Degeneration By Adenosinementioning

confidence: 99%

Purinergic signaling in retinal degeneration and regeneration

Reichenbach

Bringmann

2016

Neuropharmacology

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“…101 BzATP also kills RGCs in vivo ; this death is inhibited by P2X7R blockers MRS 2540 and Brilliant blue G. 102 This suggests that the mechanosensitive release of ATP accompanying elevation of IOP may influence ganglion cell health in acute and chronic glaucoma. 103,104 …”

Section: Mechanosensitive Release Of Atp Via Pannexins and Autostimulmentioning

confidence: 99%

From Mechanosensitivity to Inflammatory Responses: New Players in the Pathology of Glaucoma

Križaj

Ryskamp

Tian

et al. 2013

Current Eye Research

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142

132

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Purpose of the study Many blinding diseases of the inner retina are associated with degeneration and loss of retinal ganglion cells (RGCs). Recent evidence implicates several new signaling mechanisms as causal agents associated with RGC injury and remodeling of the optic nerve head. Ion channels such as Transient receptor potential vanilloid isoform 4 (TRPV4), pannexin-1 (Panx1) and P2X7 receptor are localized to RGCs and act as potential sensors and effectors of mechanical strain, ischemia and inflammatory responses. Under normal conditions, TRPV4 may function as an osmosensor and a polymodal molecular integrator of diverse mechanical and chemical stimuli, whereas P2X7R and Panx1 respond to stretch- and/or swelling-induced adenosine triphosphate release from neurons and glia. Ca2+ influx, induced by stimulation of mechanosensitive ion channels in glaucoma, is proposed to influence dendritic and axonal remodeling that may lead to RGC death while (at least initially) sparing other classes of retinal neuron. The secondary phase of the retinal glaucoma response is associated with microglial activation and an inflammatory response involving Toll-like receptors (TLRs), cluster of differentiation 3 (CD3) immune recognition molecules associated with the T-cell antigen receptor, complement molecules and cell type-specific release of neuroactive cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). The retinal response to mechanical stress thus involves a diversity of signaling pathways that sense and transduce mechanical strain and orchestrate both protective and destructive secondary responses. Conclusions Mechanistic understanding of the interaction between pressure-dependent and independent pathways is only beginning to emerge. This review focuses on the molecular basis of mechanical strain transduction as a primary mechanism that can damage RGCs. The damage occurs through Ca2+-dependent cellular remodeling and is associated with parallel activation of secondary ischemic and inflammatory signaling pathways. Molecules that mediate these mechanosensory and immune responses represent plausible targets for protecting ganglion cells in glaucoma, optic neuritis and retinal ischemia.

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“…They are functionally expressed by retinal ganglion cells [2–10] and Müller glial cells [11], and their presence on amacrine, horizontal [7, 12, 13] and microglial cells [4, 7] has also been suggested. The upregulation of P2X 7 R expression and activation by extracellular ATP is associated with the elevation of intracellular calcium and subsequent photoreceptor and retinal ganglion cell (RGC) death, thus implicating a role for P2X 7 Rs in retinal degenerations such as retinitis pigmentosa, glaucoma, age-related macular degeneration (AMD) and retinopathies [14, 15]. …”

Section: Introductionmentioning

confidence: 99%

P2X7R modulation of visually evoked synaptic responses in the retina

Chavda¹,

Luthert

Salt³

2016

Purinergic Signalling

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P2X7Rs are distributed throughout all layers of the retina, and thus, their localisation on various cell types puts into question their specific site(s) of action. Using a dark-adapted, ex vivo mouse retinal whole mount preparation, the present study aimed to characterise the effect of P2X7R activation on light-evoked, excitatory RGC ON-field excitatory post-synaptic potentials (fEPSPs) and on outer retinal electroretinogram (ERG) responses under comparable conditions. The pharmacologically isolated NMDA receptor-mediated RGC ON-fEPSP was reduced in the presence of BzATP, an effect which was significantly attenuated by A438079 and other selective P2X7R antagonists A804598 or AF27139. In physiological Krebs medium, BzATP induced a significant potentiation of the ERG a-wave, with a concomitant reduction in the b-wave and the power of the oscillatory potentials. Conversely, in the pharmacologically modified Mg2+-free perfusate, BzATP reduced both the a-wave and b-wave. The effects of BzATP on the ERG components were suppressed by A438079. A role for P2X7R function in visual processing in both the inner and outer retina under physiological conditions remains controversial. The ON-fEPSP was significantly reduced in the presence of A804598 but not by A438079 or AF27139. Furthermore, A438079 did not have any effect on the ERG components in physiological Krebs but potentiated and reduced the a-wave and b-wave, respectively, when applied to the pharmacologically modified medium. Therefore, activation of P2X7Rs affects the function in the retinal ON pathway. The presence of a high concentration of extracellular ATP would most likely contribute to the modulation of visual transmission in the retina in the pathophysiological microenvironment.

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The P2X7 receptor in retinal ganglion cells: A neuronal model of pressure-induced damage and protection by a shifting purinergic balance

Cited by 45 publications

References 53 publications

Purinergic signaling in retinal degeneration and regeneration

Purinergic signaling in retinal degeneration and regeneration

From Mechanosensitivity to Inflammatory Responses: New Players in the Pathology of Glaucoma

P2X7R modulation of visually evoked synaptic responses in the retina

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