PMID- 27799744
OWN - NLM
STAT- MEDLINE
DCOM- 20170508
LR  - 20181113
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 10
DP  - 2016
TI  - alpha-Aminoadipic acid protects against retinal disruption through attenuating Muller 
      cell gliosis in a rat model of acute ocular hypertension.
PG  - 3449-3457
AB  - OBJECTIVE: Ocular hypertension is an important risk factor for glaucoma. The 
      purpose of this study was to investigate the gliotoxic effects of alpha-aminoadipic 
      acid (AAA) in a rat model of AOH and its underlying mechanisms. MATERIALS AND 
      METHODS: In the rat model of acute ocular hypertension (AOH), intraocular 
      pressure was increased to 110 mmHg for 60 minutes. Animals were divided into four 
      groups: sham operation (Ctrl), AOH, AOH + phosphate-buffered saline (PBS), and 
      AOH + AAA. Cell apoptosis in the ganglion cell layer was detected with the 
      terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin 
      nick end labeling (TUNEL) assay, and retinal ganglion cells (RGCs) immunostained 
      with Thy-1 were counted. Muller cell activation was detected using immunostaining 
      with glutamine synthetase and glial fibrillary acidic protein. Tumor necrosis 
      factor-alpha (TNF-alpha) was examined using Western blot. RESULTS: In the rat model of 
      AOH, cell apoptosis was induced in the ganglion cell layer and the number of RGCs 
      was decreased. Muller cell gliosis in the retinas of rats was induced, and 
      retinal protein levels of TNF-alpha were increased. Intravitreal treatment of AAA 
      versus PBS control attenuated these retinal abnormalities to show protective 
      effects in the rat model of AOH. CONCLUSION: In the retinas of the rat model of 
      AOH, AAA treatment attenuated retinal apoptosis in the ganglion cell layer and 
      preserved the number of RGCs, likely through the attenuation of Muller cell 
      gliosis and suppression of TNF-alpha induction. Our observations suggest that AAA 
      might be a potential therapeutic target in glaucoma.
FAU - Wang, Xiaolei
AU  - Wang X
AD  - Department of Ophthalmology, Beijing Friendship Hospital; Department of 
      Neurobiology, Beijing Institute for Brain Disorders, Capital Medical University, 
      Beijing.
FAU - Su, Jier
AU  - Su J
AD  - Department of Neurobiology, Beijing Institute for Brain Disorders, Capital 
      Medical University, Beijing; Ningbo College of Health Sciences, Ningbo.
FAU - Ding, Jingwen
AU  - Ding J
AD  - Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical 
      University, Beijing.
FAU - Han, Song
AU  - Han S
AD  - Department of Neurobiology, Beijing Institute for Brain Disorders, Capital 
      Medical University, Beijing.
FAU - Ma, Wei
AU  - Ma W
AD  - Department of Neurobiology, Beijing Institute for Brain Disorders, Capital 
      Medical University, Beijing; Beijing Stomatological Hospital, Capital Medical 
      University, Beijing, People's Republic of China.
FAU - Luo, Hong
AU  - Luo H
AD  - Department of Neurobiology, Beijing Institute for Brain Disorders, Capital 
      Medical University, Beijing.
FAU - Hughes, Guy
AU  - Hughes G
AD  - University of California, Irvine School of Medicine, Irvine, CA, USA.
FAU - Meng, Zhaoyang
AU  - Meng Z
AD  - Department of Ophthalmology, Beijing Friendship Hospital.
FAU - Yin, Yi
AU  - Yin Y
AD  - Department of Ophthalmology, Beijing Friendship Hospital.
FAU - Wang, Yanling
AU  - Wang Y
AD  - Department of Ophthalmology, Beijing Friendship Hospital.
FAU - Li, Junfa
AU  - Li J
AD  - Department of Neurobiology, Beijing Institute for Brain Disorders, Capital 
      Medical University, Beijing.
LA  - eng
PT  - Journal Article
DEP - 20161020
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1K7B1OED4N (2-Aminoadipic Acid)
SB  - IM
MH  - 2-Aminoadipic Acid/chemistry/*pharmacology
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Disease Models, Animal
MH  - Ependymoglial Cells/*drug effects/pathology
MH  - Gliosis/drug therapy/*prevention & control
MH  - Male
MH  - Ocular Hypertension/*drug therapy/metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retina/*drug effects/metabolism/pathology
MH  - Retinal Ganglion Cells/*drug effects/pathology
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC5076852
OTO - NOTNLM
OT  - Muller cells
OT  - TNF-alpha
OT  - acute ocular hypertension
OT  - glaucoma
OT  - retina
OT  - retinal ganglion cells
OT  - alpha-aminoadipic acid
COIS- The authors report no conflicts of interest in this work.
EDAT- 2016/11/02 06:00
MHDA- 2017/05/10 06:00
PMCR- 2016/10/20
CRDT- 2016/11/02 06:00
PHST- 2016/11/02 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
PHST- 2016/11/02 06:00 [entrez]
PHST- 2016/10/20 00:00 [pmc-release]
AID - dddt-10-3449 [pii]
AID - 10.2147/DDDT.S105362 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2016 Oct 20;10:3449-3457. doi: 10.2147/DDDT.S105362. 
      eCollection 2016.