TrkB Signaling in Retinal Glia Stimulates Neuroprotection after Optic Nerve Injury.

Abstract

Brain-derived neurotrophic factor (BDNF) regulates neural cell survival mainly by activating TrkB receptors. Several lines of evidence support a key role for BDNF-TrkB signaling in survival of adult retinal ganglion cells in animal models of optic nerve injury (ONI), but the neuroprotective effect of exogenous BDNF is transient. Glial cells have recently attracted considerable attention as mediators of neural cell survival, and TrkB expression in retinal glia suggests its role in neuroprotection. To elucidate this point directly, we examined the effect of ONI on TrkB(flox/flox):glial fibrillary acidic protein (GFAP)-Cre+ (TrkB(GFAP)) knockout (KO) mice, in which TrkB is deleted in retinal glial cells. ONI markedly increased mRNA expression levels of basic fibroblast growth factor (bFGF) in wild-type (WT) mice but not in TrkB(GFAP) KO mice. Immunohistochemical analysis at 7 days after ONI (d7) revealed bFGF up-regulation mainly occurred in Müller glia. ONI-induced retinal ganglion cell loss in WT mice was consistently mild compared with TrkB(GFAP) KO mice at d7. On the other hand, ONI severely decreased TrkB expression in both WT and TrkB(GFAP) KO mice after d7, and the severity of retinal degeneration was comparable with TrkB(GFAP) KO mice at d14. Our data provide direct evidence that glial TrkB signaling plays an important role in the early stage of neural protection after traumatic injury.

• Authors: Chikako Harada, Yuriko Azuchi, Takahiko Noro, Xiaoli Guo, Atsuko Kimura, Kazuhiko Namekata, Takayuki Harada
• Journal: The American journal of pathology (Am J Pathol) Vol. 185 Issue 12 Pg. 3238-47 (Dec 2015) ISSN: 1525-2191 [Electronic] United States
• PMID: 26476348 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Nerve Growth Factors
• Receptor, trkB

Topics

• Animals
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Nerve Growth Factors (biosynthesis)
• Neuroglia (metabolism)
• Neuroprotection (physiology)
• Optic Nerve Injuries (complications, metabolism, pathology)
• Receptor, trkB (physiology)
• Retinal Degeneration (etiology, metabolism)
• Retinal Ganglion Cells (metabolism)
• Signal Transduction (physiology)