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The Journal of Neuroscience, July 12, 2006, 26(28):7532-7540; doi:10.1523/JNEUROSCI.1004-06.2006

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Neurobiology of Disease
Epidermal Growth Factor Receptor Activation: An Upstream Signal for Transition of Quiescent Astrocytes into Reactive Astrocytes after Neural Injury

Bin Liu,¹ Huiyi Chen,¹ Terrance G. Johns,² and Arthur H. Neufeld¹

¹Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, and ²Ludwig Institute for Cancer Research, Austin Hospital, Heidelberg 3084, Australia

Correspondence should be addressed to Dr. Bin Liu, Department of Ophthalmology, Northwestern University School of Medicine, 303 East Superior, Tarry 13-752, Chicago, IL 60611. Email: b-liu{at}northwestern.edu

Modulating the behaviors of reactive astrocytes is a potential therapeutic strategy for neurodegenerative diseases. We found that upregulation and activation of the epidermal growth factor receptor (EGFR) occur in astrocytes after different injuries in optic nerves in vivo. Activation of EGFR regulates genes and cellular processes representing most major markers of reactive astrocytes and genes related with glaucomatous optic neuropathy and other neural disorders. These results suggest that activation of EGFR is a common, regulatory pathway that triggers quiescent astrocytes into reactive astrocytes in response to neural injuries in the optic nerve, and perhaps other parts of the CNS. Targeting EGFR activation using an EGFR tyrosine kinase inhibitor prevents the loss of retinal ganglion cells in a model of glaucomatous optic neuropathy. Because these inhibitors are currently used clinically, our results present an approach to reactive astrocytes as a potential new target for the treatment of neurodegenerations.

Key words: astrocyte; epidermal growth factor receptor; neural injury; neurodegeneration; gene microarray; optic nerve

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Received March 7, 2006; revised May 25, 2006; accepted June 7, 2006.

Correspondence should be addressed to Dr. Bin Liu, Department of Ophthalmology, Northwestern University School of Medicine, 303 East Superior, Tarry 13-752, Chicago, IL 60611. Email: b-liu{at}northwestern.edu

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