Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 185, Issue 12, Pages 3238-3247Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2015.08.005
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [25462766, 25430082, 26861479, 256400043, 26640048, 15H04999]
- Funding Program for Next Generation World-Leading Researchers (NEXT Program) [LS133]
- Uehara Memorial Foundation
- Grants-in-Aid for Scientific Research [15H04999, 26640048, 26861479, 25430082, 25462766] Funding Source: KAKEN
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Brain-derived neurotrophic factor (BDNF) regulates neural cell survival mainly by activating TrkB receptors. Several tines 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 Muller 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.
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