March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Attenuated Glial Activation After Optic Nerve Crush In Bax-deficient Mice
Author Affiliations & Notes
  • Caitlin E. Mac Nair
    Ophthalmology and Visual Sciences, Univeristy of Wisconsin, Madison, Wisconsin
  • Cassandra L. Schlamp
    Ophthalmology and Visual Sciences, Univeristy of Wisconsin, Madison, Wisconsin
  • Robert W. Nickells
    Ophthalmology and Visual Sciences, Univeristy of Wisconsin, Madison, Wisconsin
  • Footnotes
    Commercial Relationships  Caitlin E. Mac Nair, None; Cassandra L. Schlamp, None; Robert W. Nickells, None
  • Footnotes
    Support  R01 EY012223, P30 EY016665, RPB
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 3871. doi:
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      Caitlin E. Mac Nair, Cassandra L. Schlamp, Robert W. Nickells; Attenuated Glial Activation After Optic Nerve Crush In Bax-deficient Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3871.

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

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Purpose: : Bax-deficient retinal ganglion cells are completely resistant to acute optic nerve crush-induced damage. Models of secondary degeneration after acute optic nerve damage predict that apoptosis-inducing cytokines are produced by retinal glia reacting to ganglion cells undergoing primary degeneration. Since these cytokines should activate extrinsic apoptosis (Bax-independent), we investigated the level of glia reaction, cytokine expression, and susceptibility of ganglion cells to select inflammatory cytokines in Bax-deficient mice.

Methods: : Bax-deficient and wild type C57BL/6 mice were compared in this study. mRNA and protein levels of glial reactivity markers and cytokine production were monitored by qPCR and ELISA assays, respectively. Glial markers used were GFAP for macroglia and Aif1 for microglia, and proinflammatory cytokines monitored included IL1b, IL6, and TNF. Experiments to directly test Bax-deficient ganglion cell susceptibility to these cytokines are underway and will be reported.

Results: : Bax-deficient mice are completely resistant to optic nerve crush, but still exhibit early onset ganglion cell atrophy such as nuclear shrinkage and loss of normal ganglion cell-specific gene expression. Glial activity is greatly diminished in Bax-deficient mice compared to wild-type mice, with a modest increase in GFAP and Aif1 mRNA levels by 2 weeks following crush injury. In wild type mice, GFAP protein levels rise over the course of 2 weeks and remained elevated after 7 days. IL6 and TNF mRNA levels were low in Bax-deficient and wild-type mice at 1 and 2 weeks post-crush, however in wild type mice IL6 proteins spiked within 24 hours, returning to normal levels by 1 week. IL1b mRNA was elevated in both Bax-deficient and wild-type mice at 1 week, and at 2 weeks remained elevated in Bax-deficient mice while dropping in wild type mice. qPCR results indicate that reactivity of both macro and microglia are substantially muted after optic nerve crush in Bax-deficient mice. Similarly, preliminary experiments suggest no changes in expression of inflammatory cytokines.

Conclusions: : While Bax-deficient ganglion cells undergo early onset atrophy and loss of gene expression after optic nerve crush, activation of glial cells in response to damage appears to require complete execution of ganglion cells subjected to the primary damaging stimulus. These results provide a framework to interrogate the mechanisms of glial activation and secondary degeneration.

Keywords: retinal glia • cytokines/chemokines • apoptosis/cell death 

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