PMID- 30993644
OWN - NLM
STAT- MEDLINE
DCOM- 20191210
LR  - 20200225
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 68
IP  - 3
DP  - 2019 Jul
TI  - PACAP Attenuates Optic Nerve Crush-Induced Retinal Ganglion Cell Apoptosis Via 
      Activation of the CREB-Bcl-2 Pathway.
PG  - 475-484
LID - 10.1007/s12031-019-01309-9 [doi]
AB  - Retinal ganglion cell (RGC) apoptosis is considered an important pathological 
      hallmark of glaucoma. Pituitary adenylate cyclase-activating polypeptide (PACAP) 
      is a pleiotropic peptide with potent neuroprotective properties. In our previous 
      study, we found that the expression of PACAP and its high-affinity receptor PACAP 
      receptor type 1 (PAC1R) increased markedly after optic nerve crush (ONC), and 
      occurred mainly in the ganglion cell layer of the retina. This suggests that the 
      upregulation of PACAP may play a vital role in inhibiting RGC death after ONC. 
      Therefore, in the present study, we investigate the specific effects and 
      underlying mechanism of PACAP in RGC death after ONC. Vehicle (physiological 
      saline) or PACAP (1 nM to 200 nM) solution was injected into the vitreous body. 
      Seven days later, the retinas were harvested, and the surviving RGCs were 
      retrogradely labeled with Fluoro-Gold (FG; Fluorochrome) at different 
      concentrations of PACAP. Immunofluorescence double staining and terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were 
      used to observe the effects of PACAP on RGC apoptosis. Our results showed that 
      PACAP treatment inhibited caspase-3-mediated RGC apoptosis, promoted the 
      phosphorylation of cAMP response element binding protein (CREB), up-regulated the 
      expression of B-cell lymphoma 2 (Bcl-2), and ultimately improved RGC survival. 
      These results suggest that PACAP may prevent RGC apoptosis after ONC via 
      activation of CREB-mediated Bcl-2 transcription. The study thus contributes to a 
      basic understanding of the mechanism by which PACAP decreased RGC apoptosis and 
      provides a theoretical basis for future clinical application of PACAP in the 
      treatment of glaucoma.
FAU - Ye, Dan
AU  - Ye D
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, 7 Jinsui Road, Guangzhou, 510623, China.
FAU - Shi, Yuxun
AU  - Shi Y
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, 7 Jinsui Road, Guangzhou, 510623, China.
FAU - Xu, Yue
AU  - Xu Y
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, 7 Jinsui Road, Guangzhou, 510623, China.
FAU - Huang, Jingjing
AU  - Huang J
AUID- ORCID: 0000-0002-3009-8681
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, 7 Jinsui Road, Guangzhou, 510623, China. hjjing@mail.sysu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20190416
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Bcl2 protein, rat)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Male
MH  - Nerve Crush
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Optic Atrophy/*drug therapy
MH  - Pituitary Adenylate Cyclase-Activating Polypeptide/*pharmacology/therapeutic use
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinal Ganglion Cells/*drug effects/metabolism/pathology
MH  - Signal Transduction
OTO - NOTNLM
OT  - Apoptosis
OT  - CREB
OT  - Optic nerve crush
OT  - PACAP
OT  - Retinal ganglion cells
EDAT- 2019/04/18 06:00
MHDA- 2019/12/18 06:00
CRDT- 2019/04/18 06:00
PHST- 2019/01/02 00:00 [received]
PHST- 2019/03/20 00:00 [accepted]
PHST- 2019/04/18 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/04/18 06:00 [entrez]
AID - 10.1007/s12031-019-01309-9 [pii]
AID - 10.1007/s12031-019-01309-9 [doi]
PST - ppublish
SO  - J Mol Neurosci. 2019 Jul;68(3):475-484. doi: 10.1007/s12031-019-01309-9. Epub 
      2019 Apr 16.