PMID- 24398098
OWN - NLM
STAT- MEDLINE
DCOM- 20140414
LR  - 20140204
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 55
IP  - 2
DP  - 2014 Feb 3
TI  - Retrograde neurotrophic signaling in rat retinal ganglion cells is transmitted 
      via the ERK5 but not the ERK1/2 pathway.
PG  - 658-65
LID - 10.1167/iovs.13-12985 [doi]
AB  - PURPOSE: Neurotrophic deprivation is considered an important event in 
      glaucomatous retinal ganglion cell (RGC) death. However, the mitogen-activated 
      protein kinase (MAPK) pathway transmitting axonal neurotrophic signals in RGC has 
      not been identified. We investigated the involvement of ERK5 and ERK1/2 in 
      retrograde axonal neurotrophic signaling in rats. METHODS: Adult Sprague-Dawley 
      rats were used. Retinal immunostaining for ERK5 and MEK5 was performed. Levels of 
      total and phosphorylated ERK5 and ERK1/2 were analyzed in retinal lysate by 
      quantitative Western blotting. The effects of age, brain-derived neurotrophic 
      factor (BDNF) stimulation at RGC soma (intravitreal injection) or axon ending 
      (superior colliculus [SC] injection), axonal tyrosine kinase receptor (Trk) 
      receptor inhibition with genistein, and acute axonal damage by optic nerve 
      transection (ONT) were investigated at time points from 24 hours to 5 days. 
      RESULTS: ERK5 and MEK5 were present in RGCs and glial cells. Phospho-ERK5 levels 
      increased in retina and decreased in brain with age (n = 4; P = 0.039). 
      Phosphorylation of ERK5 but not ERK1/2 was increased or decreased by SC injection 
      of BDNF or genistein, respectively (BDNF at 48 hours [p-ERK5: P = 0.01; p-ERK1/2: 
      P = 0.55, n = 8]; genistein at 48 hours [p-ERK5: P = 0.01; p-ERK1/2: P = 0.5, n = 
      5]). ONT showed a similar trend. BDNF stimulation at the RGC soma increased both 
      p-ERK5 and p-ERK1/2 (P = 0.035 and P = 0.032, respectively; n = 6; at 48 hours). 
      CONCLUSIONS: ERK5 is present in RGCs. Retina and brain p-ERK5 levels develop 
      differently with age. The response of ERK5 but not ERK1/2 to BDNF stimulation or 
      inhibition at the RGC axon ending indicates that retrograde neurotrophic signals 
      in the rat optic nerve may be mediated by the ERK5 pathway.
FAU - van Oterendorp, Christian
AU  - van Oterendorp C
AD  - Department of Ophthalmology, Georg-August-University Hospital, Gottingen, 
      Germany.
FAU - Sgouris, Stavros
AU  - Sgouris S
FAU - Schallner, Nils
AU  - Schallner N
FAU - Biermann, Julia
AU  - Biermann J
FAU - Lagreze, Wolf A
AU  - Lagreze WA
LA  - eng
PT  - Journal Article
DEP - 20140203
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 7)
SB  - IM
MH  - Aging/physiology
MH  - Animals
MH  - Blotting, Western
MH  - Brain/enzymology
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Intravitreal Injections
MH  - MAP Kinase Signaling System/*physiology
MH  - Male
MH  - Mitogen-Activated Protein Kinase 1/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/*metabolism
MH  - Mitogen-Activated Protein Kinase 7/*metabolism
MH  - Neuroglia/drug effects/enzymology
MH  - Optic Nerve Injuries
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retina/enzymology
MH  - Retinal Ganglion Cells/*drug effects/enzymology
MH  - Superior Colliculi/drug effects
OTO - NOTNLM
OT  - extracellular signal-regulated kinase
OT  - mitogen-activated protein kinase
OT  - optic nerve
OT  - rat
OT  - retinal ganglion cell
EDAT- 2014/01/09 06:00
MHDA- 2014/04/15 06:00
CRDT- 2014/01/09 06:00
PHST- 2014/01/09 06:00 [entrez]
PHST- 2014/01/09 06:00 [pubmed]
PHST- 2014/04/15 06:00 [medline]
AID - iovs.13-12985 [pii]
AID - 10.1167/iovs.13-12985 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2014 Feb 3;55(2):658-65. doi: 10.1167/iovs.13-12985.