Immunocytochemical localization of NTPDases1 and 2 in the neural retina of mouse and zebrafish

Ricatti, Maria Jimena; Alfie, Lionel D.; Lavoie, Élise G.; Sévigny, Jean; Schwarzbaum, Pablo J.; Faillace, María Paula

doi:10.1002/syn.20605

Cited by 32 publications

(33 citation statements)

References 64 publications

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“…Once released into the extracellular space, ATP is rapidly degraded by ectonucleotidases to ADP and/or AMP and then further degraded to adenosine [49]. In the retina, there is evidence for ectonucleotidase degradation of ATP at synaptic terminals [23] and both NTPDases1 and 2 have been found to be expressed immunocytochemically [50]. These findings support the hypothesis that ATP acts as a neurotransmitter, which may act at P2X7-Rs in the mouse retina.…”

Section: Discussionsupporting

confidence: 70%

Rod and Cone Pathway Signalling Is Altered in the P2X7 Receptor Knock Out Mouse

Vessey

Fletcher

2012

PLoS ONE

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The P2X7 receptor (P2X7-R) is expressed in the retina and brain and has been implicated in neurodegenerative diseases. However, whether it is expressed by neurons and plays a role as a neurotransmitter receptor has been the subject of controversy. In this study, we first show that the novel vesicular transporter for ATP, VNUT, is expressed in the retina, verifying the presence of the molecular machinery for ATP to act as neurotransmitter at P2X7-Rs. Secondly we show the presence of P2X7-R mRNA and protein in the retina and cortex and absence of the full length variant 1 of the receptor in the P2X7-R knock out (P2X7-KO) mouse. The role of the P2X7-R in neuronal function of the retina was assessed by comparing the electroretinogram response of P2X7-KO with WT mice. The rod photoreceptor response was found to be similar, while both rod and cone pathway post-photoreceptor responses were significantly larger in P2X7-KO mice. This suggests that activation of P2X7-Rs modulates output of second order retinal neurons. In line with this finding, P2X7-Rs were found in the outer plexiform layer and on inner retinal cell classes, including horizontal, amacrine and ganglion cells. The receptor co-localized with conventional synapses in the IPL and was expressed on amacrine cells post-synaptic to rod bipolar ribbon synapses. In view of the changes in visual function in the P2X7-KO mouse and the immunocytochemical location of the receptor in the normal retina, it is likely the P2X7-R provides excitatory input to photoreceptor terminals or to inhibitory cells that shape both the rod and cone pathway response.

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Section: Discussionsupporting

confidence: 70%

Rod and Cone Pathway Signalling Is Altered in the P2X7 Receptor Knock Out Mouse

Vessey

Fletcher

2012

PLoS ONE

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“…(G) ADA-IR colocalized with the GluR2-IR (green), indicating that ADA (red) is expressed on HC dendrites. Expression of ecto-ATPases in the photoreceptor synaptic terminal has been observed previously in rat [39], mouse, and zebrafish [61]. Scale bars in panels A, D, E, F, and G indicate 5 µm.…”

Section: Resultssupporting

confidence: 56%

“…The primary antibody against NTPDase1 was raised in rabbit to the corresponding amino acid sequence 102–130 of human NTPDase1 (GIYLTDCMERAREVIPRSQHQETPVYLGA). It was obtained from CHUQ (www.ectonucleotidases-ab.com) and characterized by Ricattie et al [61]. The ADA (AB176) and GluR2 antibodies were purchased from Chemicon International (Temecula, CA).…”

Section: Methodsmentioning

confidence: 99%

Extracellular ATP Hydrolysis Inhibits Synaptic Transmission by Increasing pH Buffering in the Synaptic Cleft

et al. 2014

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“…While the cells responsible for this release in vivo are unknown, several possibilities exist. The pattern of immunohistochemical staining in Figure 6D suggests that NTPDase1 was predominantly elevated in endothelial cells, with light staining on nerves and glial cells, consistent with findings in brain and retina, 42,[48][49][50] although precise cellular FIGURE 5. Intraocular pressure elevation in primate eyes with experimental glaucoma.…”

Section: Discussionmentioning

confidence: 51%

Rat, Mouse, and Primate Models of Chronic Glaucoma Show Sustained Elevation of Extracellular ATP and Altered Purinergic Signaling in the Posterior Eye

Sévigny

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Citation: Lu W, Hu H, Sévigny J, et al. Rat, mouse, and primate models of chronic glaucoma show sustained elevation of extracellular ATP and altered purinergic signaling in the posterior eye. Invest Ophthalmol Vis Sci. 2015;56:3075-3083. DOI:10.1167/iovs.14-15891 PURPOSE. The cellular mechanisms linking elevated IOP with glaucomatous damage remain unresolved. Mechanical strains and short-term increases in IOP can trigger ATP release from retinal neurons and astrocytes, but the response to chronic IOP elevation is unknown. As excess extracellular ATP can increase inflammation and damage neurons, we asked if sustained IOP elevation was associated with a sustained increase in extracellular ATP in the posterior eye. METHODS.No ideal animal model of chronic glaucoma exists, so three different models were used. Tg-Myoc Y437H mice were examined at 40 weeks, while IOP was elevated in rats following injection of hypertonic saline into episcleral veins and in cynomolgus monkeys by laser photocoagulation of the trabecular meshwork. The ATP levels were measured using the luciferin-luciferase assay while levels of NTPDase1 were assessed using qPCR, immunoblots, and immunohistochemistry.RESULTS. The ATP levels were elevated in the vitreal humor of rats, mice, and primates after a sustained period of IOP elevation. The ecto-ATPase NTPDase1 was elevated in optic nerve head astrocytes exposed to extracellular ATP for an extended period. NTPDase1 was also elevated in the retinal tissue of rats, mice, and primates, and in the optic nerve of rats, with chronic elevation in IOP. CONCLUSIONS.A sustained elevation in extracellular ATP, and upregulation of NTPDase1, occurs in the posterior eye of rat, mouse, and primate models of chronic glaucoma. This suggests the elevation in extracellular ATP may be sustained in chronic glaucoma, and implies a role for altered purinergic signaling in the disease.Keywords: ATP release, mechanosensitive, retina G laucoma is one of the leading causes of blindness in humans and is characterized by damage to retinal ganglion cells (RGCs) and the optic nerve.1,2 While abnormally high IOP is a widely recognized risk factor, 3,4 the molecular pathways linking elevated IOP and RGC loss are complex. Although several inroads toward understanding the mechanisms have recently been made, 5-13 much remains to be learned, particularly regarding the responses in chronic injury. Extracellular ATP is a likely candidate to link the elevated IOP in glaucoma to perturbed signaling in the retina and optic nerve. Throughout the body, released ATP conveys information about mechanical strain and accompanies shear stress, swelling, and stretch. [14][15][16][17][18] This mechanosensitive release of ATP can initiate a series of physiological and pathological responses including cell death, volume regulation, pain, inflammatory responses, and neuroprotection by activating ionotropic P2X and metabotropic P2Y receptors. 19Evidence is accumulating for an increased release of ATP following IOP elevation in glaucoma. For instance...

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Immunocytochemical localization of NTPDases1 and 2 in the neural retina of mouse and zebrafish

Cited by 32 publications

References 64 publications

Rod and Cone Pathway Signalling Is Altered in the P2X7 Receptor Knock Out Mouse

Rod and Cone Pathway Signalling Is Altered in the P2X7 Receptor Knock Out Mouse

Extracellular ATP Hydrolysis Inhibits Synaptic Transmission by Increasing pH Buffering in the Synaptic Cleft

Rat, Mouse, and Primate Models of Chronic Glaucoma Show Sustained Elevation of Extracellular ATP and Altered Purinergic Signaling in the Posterior Eye

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