June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Adenosine triphosphate (ATP) Signaling Pathways Trigger Glial Activation in the Mouse Retina
Author Affiliations & Notes
  • Caitlin Mac Nair
    Cellular and Molecular Pathology Graduate Program, Univeristy of Wisconsin, Madison, WI
    Ophthalmology and Visual Sciences, Univeristy of Wisconsin, Madison, WI
  • Cassandra Schlamp
    Ophthalmology and Visual Sciences, Univeristy of Wisconsin, Madison, WI
  • Robert Nickells
    Ophthalmology and Visual Sciences, Univeristy of Wisconsin, Madison, WI
  • Footnotes
    Commercial Relationships Caitlin Mac Nair, None; Cassandra Schlamp, None; Robert Nickells, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 286. doi:
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      Caitlin Mac Nair, Cassandra Schlamp, Robert Nickells; Adenosine triphosphate (ATP) Signaling Pathways Trigger Glial Activation in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):286.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Optic nerve injury causes RGC death and activation of the retinal macroglia and microglia. Bax-deficient RGCs are resistant to this acute injury and display an attenuated glial activation response, indicating a relationship between cell death and glial activation. Several studies suggest that injured neurons release ATP as a distress signal, and we investigated the potential role of ATP in triggering glial activation, the consequence of which may lead to cytokine production that damages additional ganglion cells.

Methods: Wild type mice were intravitreally injected with 1μl of a 250μM ATP receptor agonist, either ATPγS or BzATP, and mRNA and protein levels of glial activation markers (GFAP for macroglia and AIF1 for microglia) were monitored by qPCR and immunofluorescence. RGC gene markers Thy1, Nrn1, and Sncg were also monitored by qPCR. Additional experiments will include Bax-deficient mice injected with either BzATP or ATPγS, and wild type mice treated with an ATP receptor antagonist, either oxATP or PPADS, to inhibit ATP signaling from crush injury. The effects on glial activation and RGC survival will be reported.

Results: Bax-deficient RGCs were completely resistant to optic nerve crush and displayed an attenuated macroglial and microglial activation response, suggesting that cell death is required for glial activation. A single intravitreal injection of BzATP, a specific P2X7 receptor agonist, caused a significant spike in macroglial activation by 24 hours with prominent labeling in the Müller cells. By 48 hours macroglial activation returned to basal levels and remained unchanged by 72 hours. Contrary, macroglial activation by the broad spectrum P2X receptor agonist, ATPγS, showed a moderate increase at 24 hours above vehicle-injected eyes but continued to rise at 48 and 72 hours, with strong labeling of the Müller cells by 72 hours. A decline in RGC gene markers, indicative of RGC damage, was also apparent at 72 hours in ATPγS-injected eyes. Microglial activation was not greatly affected by either treatment.

Conclusions: These results indicate that ATP may contribute to macroglial activation during glaucoma. The sustained elevation of ATPγS over BzATP at 72 hours suggests that purinergic receptors in addition to P2X7 may be involved in triggering activation and subsequent injury to RGCs.

Keywords: 540 glia • 557 inflammation • 603 Muller cells  

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