PMID- 23383140
OWN - NLM
STAT- MEDLINE
DCOM- 20130722
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 1
DP  - 2013
TI  - Erythropoietin protects adult retinal ganglion cells against NMDA-, trophic 
      factor withdrawal-, and TNF-alpha-induced damage.
PG  - e55291
LID - 10.1371/journal.pone.0055291 [doi]
LID - e55291
AB  - PURPOSE: This study aimed to evaluate the neuroprotective effect of EPO in the 
      presence of N-methyl-d-aspartate (NMDA)-, trophic factor withdrawal (TFW)-, and 
      tumor necrosis factor-alpha (TNF-alpha)-induced toxicity on total, small, and large 
      retinal ganglion cells (RGCs). METHODS: Retinal cells from adult rats were 
      cultured in a medium containing brain-derived neurotrophic factor (BDNF), ciliary 
      neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF), and forskolin. 
      Expression of RGC markers and EPOR was examined using immunocytochemistry. RGCs 
      were classified according to their morphological properties. Cytotoxicity was 
      induced by NMDA, TFW, or TNF-alpha. RGC survival was assessed by counting thy-1 and 
      neurofilament-l double-positive cells. RESULTS: EPO offered dose-dependent 
      (EC(5)(0) = 5.7 ng/mL) protection against NMDA toxicity for small RGCs; protection 
      was not significant for large RGCs. Time-course analysis showed that the presence 
      of EPO either before or after NMDA exposure gave effective protection. For both 
      small and large RGCs undergoing trophic factor withdrawal, EPO at concentrations 
      of 1, 10, or 100 ng/mL improved survival. However, EPO had to be administered 
      soon after the onset of injury to provide effective protection. For TNF-alpha-induced 
      toxicity, survival of small RGCs was seen only for the highest examined 
      concentration (100 ng/mL) of EPO, whereas large RGCs were protected at 
      concentrations of 1, 10, or 100 ng/mL of EPO. Time-course analysis showed that 
      pretreatment with EPO provided protection only for large RGCs; early 
      post-treatment with EPO protected both small and large RGCs. Inhibitors of signal 
      transduction and activators of transcription such as (STAT)-5, mitogen-activated 
      protein kinases (MAPK)/extracellular-regulated kinase (ERK), and phosphatidyl 
      inositol-3 kinase (PI3K)/Akt impaired the protective effect of EPO on RGCs 
      exposed to different insults. CONCLUSION: EPO provided neuroprotection to 
      cultured adult rat RGCs; however, the degree of protection varied with the type 
      of toxic insult, RGC subtype, and timing of EPO treatment.
FAU - Chang, Zhi-Yang
AU  - Chang ZY
AD  - Graduate Institute of Life Sciences, National Defense Medical Center, Neihu, 
      Taipei, Taiwan.
FAU - Yeh, Ming-Kung
AU  - Yeh MK
FAU - Chiang, Chiao-Hsi
AU  - Chiang CH
FAU - Chen, Yi-Hao
AU  - Chen YH
FAU - Lu, Da-Wen
AU  - Lu DW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130130
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (Culture Media)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 11096-26-7 (Erythropoietin)
RN  - 1F7A44V6OU (Colforsin)
RN  - 6384-92-5 (N-Methylaspartate)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor
MH  - Cell Count
MH  - Cell Culture Techniques
MH  - Ciliary Neurotrophic Factor
MH  - Colforsin
MH  - Culture Media
MH  - Dose-Response Relationship, Drug
MH  - Erythropoietin/*pharmacology
MH  - Fibroblast Growth Factor 2
MH  - Immunohistochemistry
MH  - Microscopy, Fluorescence
MH  - N-Methylaspartate/*toxicity
MH  - Rats
MH  - Retinal Ganglion Cells/*cytology/*drug effects
MH  - Toxicity Tests
MH  - Tumor Necrosis Factor-alpha/*toxicity
PMC - PMC3559395
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/02/06 06:00
MHDA- 2013/07/23 06:00
PMCR- 2013/01/30
CRDT- 2013/02/06 06:00
PHST- 2012/08/26 00:00 [received]
PHST- 2012/12/20 00:00 [accepted]
PHST- 2013/02/06 06:00 [entrez]
PHST- 2013/02/06 06:00 [pubmed]
PHST- 2013/07/23 06:00 [medline]
PHST- 2013/01/30 00:00 [pmc-release]
AID - PONE-D-12-25910 [pii]
AID - 10.1371/journal.pone.0055291 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(1):e55291. doi: 10.1371/journal.pone.0055291. Epub 2013 Jan 30.