Retinal glial responses to optic nerve crush are attenuated in Bax-deficient mice and modulated by purinergic signaling pathways.

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.

• Authors: Caitlin E Mac Nair, Cassandra L Schlamp, Angela D Montgomery, Valery I Shestopalov, Robert W Nickells
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 13 Issue 1 Pg. 93 (Apr 28 2016) ISSN: 1742-2094 [Electronic] England
• PMID: 27126275 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• bcl-2-Associated X Protein

Topics

• Animals
• Disease Models, Animal
• Fluorescent Antibody Technique
• Mice
• Mice, Knockout
• Nerve Crush
• Neuroglia (metabolism, pathology)
• Optic Nerve Injuries (metabolism, pathology)
• Retinal Ganglion Cells (metabolism, pathology)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (physiology)
• bcl-2-Associated X Protein (metabolism)