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Decreased TNF levels and improved retinal ganglion cell survival in MMP-2 Null mice suggest a role for MMP-2 as TNF sheddase

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Abstract
Matrix metalloproteinases (MMPs) have been designated as both friend and foe in the central nervous system (CNS): while being involved in many neurodegenerative and neuroinflammatory diseases, their actions appear to be indispensable to a healthy CNS. Pathological conditions in the CNS are therefore often related to imbalanced MMP activities and disturbances of the complex MMP-dependent protease network. Likewise, in the retina, various studies in animal models and human patients suggested MMPs to be involved in glaucoma. In this study, we sought to determine the spatiotemporal expression profile of MMP-2 in the excitotoxic retina and to unravel its role during glaucoma pathogenesis. We reveal that intravitreal NMDA injection induces MMP-2 expression to be upregulated in the Muller glia. Moreover, MMP-2 null mice display attenuated retinal ganglion cell death upon excitotoxic insult to the retina, which is accompanied by normal glial reactivity, yet reduced TNF levels. Hence, we propose a novel in vivo function for MMP-2, as an activating sheddase of tumor necrosis factor (TNF). Given the pivotal role of TNF as a proinflammatory cytokine and neurodegeneration-exacerbating mediator, these findings generate important novel insights into the pathological processes contributing to glaucomatous neurodegeneration and into the interplay of neuroinflammation and neurodegeneration in the CNS.
Keywords
EXPERIMENTAL GLAUCOMA, MATRIX METALLOPROTEINASES, NEURODEGENERATIVE DISORDERS, DOWN-REGULATION, UP-REGULATION, MOUSE RETINA, DEATH, METHYL-D-ASPARTATE, NECROSIS-FACTOR-ALPHA, OPTIC-NERVE LIGATION

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MLA
De Groef, Lies et al. “Decreased TNF Levels and Improved Retinal Ganglion Cell Survival in MMP-2 Null Mice Suggest a Role for MMP-2 as TNF Sheddase.” MEDIATORS OF INFLAMMATION (2015): n. pag. Print.
APA
De Groef, L., Salinas-Navarro, M., Van Imschoot, G., Libert, C., Vandenbroucke, R., & Moons, L. (2015). Decreased TNF levels and improved retinal ganglion cell survival in MMP-2 Null mice suggest a role for MMP-2 as TNF sheddase. MEDIATORS OF INFLAMMATION.
Chicago author-date
De Groef, Lies, Manuel Salinas-Navarro, Griet Van Imschoot, Claude Libert, Roosmarijn Vandenbroucke, and Lieve Moons. 2015. “Decreased TNF Levels and Improved Retinal Ganglion Cell Survival in MMP-2 Null Mice Suggest a Role for MMP-2 as TNF Sheddase.” Mediators of Inflammation.
Chicago author-date (all authors)
De Groef, Lies, Manuel Salinas-Navarro, Griet Van Imschoot, Claude Libert, Roosmarijn Vandenbroucke, and Lieve Moons. 2015. “Decreased TNF Levels and Improved Retinal Ganglion Cell Survival in MMP-2 Null Mice Suggest a Role for MMP-2 as TNF Sheddase.” Mediators of Inflammation.
Vancouver
1.
De Groef L, Salinas-Navarro M, Van Imschoot G, Libert C, Vandenbroucke R, Moons L. Decreased TNF levels and improved retinal ganglion cell survival in MMP-2 Null mice suggest a role for MMP-2 as TNF sheddase. MEDIATORS OF INFLAMMATION. 2015;
IEEE
[1]
L. De Groef, M. Salinas-Navarro, G. Van Imschoot, C. Libert, R. Vandenbroucke, and L. Moons, “Decreased TNF levels and improved retinal ganglion cell survival in MMP-2 Null mice suggest a role for MMP-2 as TNF sheddase,” MEDIATORS OF INFLAMMATION, 2015.
@article{6973459,
  abstract     = {Matrix metalloproteinases (MMPs) have been designated as both friend and foe in the central nervous system (CNS): while being involved in many neurodegenerative and neuroinflammatory diseases, their actions appear to be indispensable to a healthy CNS. Pathological conditions in the CNS are therefore often related to imbalanced MMP activities and disturbances of the complex MMP-dependent protease network. Likewise, in the retina, various studies in animal models and human patients suggested MMPs to be involved in glaucoma. In this study, we sought to determine the spatiotemporal expression profile of MMP-2 in the excitotoxic retina and to unravel its role during glaucoma pathogenesis. We reveal that intravitreal NMDA injection induces MMP-2 expression to be upregulated in the Muller glia. Moreover, MMP-2 null mice display attenuated retinal ganglion cell death upon excitotoxic insult to the retina, which is accompanied by normal glial reactivity, yet reduced TNF levels. Hence, we propose a novel in vivo function for MMP-2, as an activating sheddase of tumor necrosis factor (TNF). Given the pivotal role of TNF as a proinflammatory cytokine and neurodegeneration-exacerbating mediator, these findings generate important novel insights into the pathological processes contributing to glaucomatous neurodegeneration and into the interplay of neuroinflammation and neurodegeneration in the CNS.},
  articleno    = {108617},
  author       = {De Groef, Lies and Salinas-Navarro, Manuel and Van Imschoot, Griet and Libert, Claude and Vandenbroucke, Roosmarijn and Moons, Lieve},
  issn         = {0962-9351},
  journal      = {MEDIATORS OF INFLAMMATION},
  keywords     = {EXPERIMENTAL GLAUCOMA,MATRIX METALLOPROTEINASES,NEURODEGENERATIVE DISORDERS,DOWN-REGULATION,UP-REGULATION,MOUSE RETINA,DEATH,METHYL-D-ASPARTATE,NECROSIS-FACTOR-ALPHA,OPTIC-NERVE LIGATION},
  language     = {eng},
  pages        = {13},
  title        = {Decreased TNF levels and improved retinal ganglion cell survival in MMP-2 Null mice suggest a role for MMP-2 as TNF sheddase},
  url          = {http://dx.doi.org/10.1155/2015/108617},
  year         = {2015},
}

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