Abstract
Background: Retinal ganglion cell (RGC) soma death is a consequence of optic nerve damage, including in optic neuropathies like glaucoma. The activation of the innate immune network in the retina after nerve damage has been linked to RGC pathology. Since the eye is immune privileged, innate immune functions are the responsibility of the glia, specifically the microglia, astrocytes, and Müller cells that populate the retina. Glial activation, leading to the production of inflammatory cytokines, is a hallmark feature of retinal injury resulting from optic nerve damage and purported to elicit secondary degeneration of RGC somas. Methods: A mouse model of optic nerve crush (ONC) was used to study retinal glial activation responses. RGC apoptosis was blocked using Bax-deficient mice. Glial activation responses were monitored by quantitative PCR and immunofluorescent labeling in retinal sections of activation markers. ATP signaling pathways were interrogated using P2X receptor agonists and antagonists and Pannexin 1 (Panx1)-deficient mice with RGC-specific deletion. Results: ONC induced activation of both macroglia and microglia in the retina, and both these responses were dramatically muted if RGC death was blocked by deletion of the Bax gene. Macroglial, but not microglial, activation was modulated by purinergic receptor activation. Release of ATP after optic nerve damage was not mediated by PANX1 channels in RGCs. Conclusions: RGC death in response to ONC plays a principal stimulatory role in the retinal glial activation response.
| Original language | English (US) |
|---|---|
| Article number | 93 |
| Journal | Journal of Neuroinflammation |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 28 2016 |
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Keywords
- BAX
- Macroglia
- Microglia
- Neuroinflammation
- Optic nerve damage
- P2X Receptor
- PANX1
- Retinal ganglion cell
ASJC Scopus subject areas
- Neuroscience(all)
- Cellular and Molecular Neuroscience
- Neurology
- Immunology
Cite this
Retinal glial responses to optic nerve crush are attenuated in Bax-deficient mice and modulated by purinergic signaling pathways. / Mac Nair, Caitlin E.; Schlamp, Cassandra L.; Montgomery, Angela D.; Shestopalov, Valery I; Nickells, Robert W.
In: Journal of Neuroinflammation, Vol. 13, No. 1, 93, 28.04.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Retinal glial responses to optic nerve crush are attenuated in Bax-deficient mice and modulated by purinergic signaling pathways
AU - Mac Nair, Caitlin E.
AU - Schlamp, Cassandra L.
AU - Montgomery, Angela D.
AU - Shestopalov, Valery I
AU - Nickells, Robert W.
PY - 2016/4/28
Y1 - 2016/4/28
N2 - Background: Retinal ganglion cell (RGC) soma death is a consequence of optic nerve damage, including in optic neuropathies like glaucoma. The activation of the innate immune network in the retina after nerve damage has been linked to RGC pathology. Since the eye is immune privileged, innate immune functions are the responsibility of the glia, specifically the microglia, astrocytes, and Müller cells that populate the retina. Glial activation, leading to the production of inflammatory cytokines, is a hallmark feature of retinal injury resulting from optic nerve damage and purported to elicit secondary degeneration of RGC somas. Methods: A mouse model of optic nerve crush (ONC) was used to study retinal glial activation responses. RGC apoptosis was blocked using Bax-deficient mice. Glial activation responses were monitored by quantitative PCR and immunofluorescent labeling in retinal sections of activation markers. ATP signaling pathways were interrogated using P2X receptor agonists and antagonists and Pannexin 1 (Panx1)-deficient mice with RGC-specific deletion. Results: ONC induced activation of both macroglia and microglia in the retina, and both these responses were dramatically muted if RGC death was blocked by deletion of the Bax gene. Macroglial, but not microglial, activation was modulated by purinergic receptor activation. Release of ATP after optic nerve damage was not mediated by PANX1 channels in RGCs. Conclusions: RGC death in response to ONC plays a principal stimulatory role in the retinal glial activation response.
AB - Background: Retinal ganglion cell (RGC) soma death is a consequence of optic nerve damage, including in optic neuropathies like glaucoma. The activation of the innate immune network in the retina after nerve damage has been linked to RGC pathology. Since the eye is immune privileged, innate immune functions are the responsibility of the glia, specifically the microglia, astrocytes, and Müller cells that populate the retina. Glial activation, leading to the production of inflammatory cytokines, is a hallmark feature of retinal injury resulting from optic nerve damage and purported to elicit secondary degeneration of RGC somas. Methods: A mouse model of optic nerve crush (ONC) was used to study retinal glial activation responses. RGC apoptosis was blocked using Bax-deficient mice. Glial activation responses were monitored by quantitative PCR and immunofluorescent labeling in retinal sections of activation markers. ATP signaling pathways were interrogated using P2X receptor agonists and antagonists and Pannexin 1 (Panx1)-deficient mice with RGC-specific deletion. Results: ONC induced activation of both macroglia and microglia in the retina, and both these responses were dramatically muted if RGC death was blocked by deletion of the Bax gene. Macroglial, but not microglial, activation was modulated by purinergic receptor activation. Release of ATP after optic nerve damage was not mediated by PANX1 channels in RGCs. Conclusions: RGC death in response to ONC plays a principal stimulatory role in the retinal glial activation response.
KW - BAX
KW - Macroglia
KW - Microglia
KW - Neuroinflammation
KW - Optic nerve damage
KW - P2X Receptor
KW - PANX1
KW - Retinal ganglion cell
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UR - http://www.scopus.com/inward/citedby.url?scp=84973121990&partnerID=8YFLogxK
U2 - 10.1186/s12974-016-0558-y
DO - 10.1186/s12974-016-0558-y
M3 - Article
C2 - 27126275
AN - SCOPUS:84973121990
VL - 13
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
SN - 1742-2094
IS - 1
M1 - 93
ER -