June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
An Investigation of the p38 Activator TAB1 in Glaucomatous Retina
Author Affiliations & Notes
  • Melissa Leigh Cooper
    Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, TN
  • David J Calkins
    Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, TN
    Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN
  • Footnotes
    Commercial Relationships Melissa Cooper, None; David Calkins, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2456. doi:
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      Melissa Leigh Cooper, David J Calkins; An Investigation of the p38 Activator TAB1 in Glaucomatous Retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2456.

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

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Purpose: Signaling via p38 mitogen-activated protein kinase is typically pathogenic in age-related neurodegenerative disease, coupling to various downstream inflammatory cascades. Similarly, activation of p38 is associated with degeneration of retinal ganglion cells (RGCs) in models of glaucoma, and inhibition of p38 may represent an alternative therapeutic intervention. However, p38 signaling also influences many homeostatic processes including differentiation, maturation, and neuronal remodeling for synaptic plasticity. TGF-β activated kinase 1 (TAB1) forms a complex with p38 in cardiac tissue at an allosteric site that induces a conformational change, rendering p38 more likely to activate via auto-phosphorylation to enhance pathogenic signaling. Here we investigated TAB1 in the retina and brain and whether expression changes with exposure to simple stressors.

Methods: We used immune-magnetic separation to prepare primary RGC cultures from postnatal Sprague-Dawley rat retina and maintained cells at either ambient or elevated (70mmHg) hydrostatic pressure. We used immunocytochemistry to examine levels and localization of TAB1 in these RGCs and compared the results to expression in sections of retina from C57 mice and from the DBA2J mouse model of pigmentary glaucoma (3-9 months). Signals were quantified using ImagePro software.

Results: As first described in other tissues, we find expression of TAB1 mRNA and protein in both naïve retina and brain, as confirmed using Western Blot and PCR. For isolated RGCs, TAB1 protein localized primarily in neurites with little or no expression in cell bodies; levels increased in RGCs exposed to elevated pressure for 12 hrs. In DBA2J retina, TAB1 localized primarily to Müller glia processes spanning the retina and to unmyelinated RGC axons in the nerve fiber layer and optic nerve head. Levels increased with age and elevated intraocular pressure (p=0.05). In comparison, while the pattern of TAB1 localization was similar, levels in naïve C57 mice were lower compared to all DBA2J tissue.

Conclusions: Our results demonstrate robust expression of TAB1 in retinal neurons and Müller glia and that expression is up-regulated in RGCs due to glaucoma-related stressors. This upregulation suggests that TAB1 may influence progression of neurodegeneration in glaucoma by modulating p38 phosphorylation. If so, targeting the interaction of TAB1 and p38 may provide a viable alternative for inhibiting p38 signaling.


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