PMID- 35415762
OWN - NLM
STAT- MEDLINE
DCOM- 20220608
LR  - 20220608
IS  - 1420-908X (Electronic)
IS  - 1023-3830 (Linking)
VI  - 71
IP  - 5-6
DP  - 2022 Jun
TI  - Inhibition of endoplasmic reticulum stress by 4-phenylbutyrate alleviates retinal 
      inflammation and the apoptosis of retinal ganglion cells after ocular alkali burn 
      in mice.
PG  - 577-590
LID - 10.1007/s00011-022-01565-3 [doi]
AB  - OBJECTIVE: Retinal ganglion cell (RGC) apoptosis is one of the most severe 
      complications that causes permanent visual impairment following ocular alkali 
      burn (OAB). Currently, very few treatment options exist for this condition. This 
      study was conducted to determine the effect of 4-phenylbutyric acid (4-PBA) on 
      endoplasmic reticulum (ER) stress after OAB using a well-established OAB mouse 
      model. METHODS: Ocular alkali burn was induced in C57BL/6 mouse corneas using 1 M 
      NaOH. 4-PBA (10 mg/kg; 250 muL per injection) or saline (250 muL per injection) was 
      injected intraperitoneally once per day for 3 days before the establishment of 
      the OAB model. The apoptosis of retinal ganglion cells (RGCs) was assessed by 
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      assay, and the histological damage was examined by hematoxylin and eosin and 
      immunofluorescence assay on retinal flat mounts. The key inflammatory response 
      and the expression of ER stress-related markers in the retinal tissues were 
      assessed by real-time PCR, western blotting and histologic analyses. RESULTS: 
      4-PBA significantly alleviated the apoptosis of RGCs and prevented the structural 
      damage of the retina, as determined by the evaluation of RGC density and retinal 
      thickness. Inhibition of ER stress by 4-PBA decreased the expression of vital 
      proinflammatory cytokines, tumor necrosis factor alpha, and interleukin-1 beta; 
      and suppressed the activation of retinal microglial cells and nuclear 
      factor-kappa B (NF-kappaB). 4-PBA reduced the expression of the ER stress molecules, 
      glucose-regulated protein 78, activated transcription factor 6, 
      inositol-requiring enzyme-1 (IRE1), X-box-binding protein 1 splicing, and 
      CCAAT/enhancer-binding protein homologous protein, in the retinal tissues and 
      RGCs of OAB mice. CONCLUSIONS: The present study demonstrated that the inhibition 
      of ER stress by 4-PBA alleviates the inflammatory response via the IRE1/NF-kappaB 
      signaling pathway and protects the retina and RGCs from injury in an OAB mouse 
      model. Such findings further suggest that 4-PBA might have potential therapeutic 
      implications for OAB treatment.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
FAU - Huang, Yanqiao
AU  - Huang Y
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangzhou, 510060, China.
FAU - Yuan, Miner
AU  - Yuan M
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangzhou, 510060, China.
FAU - Duan, Fang
AU  - Duan F
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangzhou, 510060, China.
FAU - Yang, Yao
AU  - Yang Y
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangzhou, 510060, China.
FAU - Lou, Bingsheng
AU  - Lou B
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangzhou, 510060, China.
FAU - Lin, Xiaofeng
AU  - Lin X
AUID- ORCID: 0000-0002-3063-9601
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangzhou, 510060, China. linxiaof@mail.sysu.edu.cn.
LA  - eng
GR  - 81974135/National Natural Science Foundation of China/
GR  - 81900851/National Natural Science Foundation of China/
GR  - 30306020240020130/Fundamental Research Funds of the State Key Laboratory of 
      Ophthalmology/
GR  - 3030902113030/Fundamental Research Funds of the State Key Laboratory of 
      Ophthalmology/
PT  - Journal Article
DEP - 20220412
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (NF-kappa B)
RN  - 0 (Phenylbutyrates)
RN  - 7WY7YBI87E (4-phenylbutyric acid)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - *Burns, Chemical/metabolism/pathology
MH  - Disease Models, Animal
MH  - *Endoplasmic Reticulum Stress
MH  - Inflammation/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Phenylbutyrates
MH  - Protein Serine-Threonine Kinases
MH  - Retinal Ganglion Cells/metabolism/pathology
OTO - NOTNLM
OT  - 4-Phenylbutyric acid
OT  - Apoptosis
OT  - Endoplasmic reticulum stress
OT  - Inflammation
OT  - Ocular alkali burn
OT  - Retinal ganglion cells
EDAT- 2022/04/14 06:00
MHDA- 2022/06/09 06:00
CRDT- 2022/04/13 05:38
PHST- 2021/08/24 00:00 [received]
PHST- 2022/03/19 00:00 [accepted]
PHST- 2022/02/28 00:00 [revised]
PHST- 2022/04/14 06:00 [pubmed]
PHST- 2022/06/09 06:00 [medline]
PHST- 2022/04/13 05:38 [entrez]
AID - 10.1007/s00011-022-01565-3 [pii]
AID - 10.1007/s00011-022-01565-3 [doi]
PST - ppublish
SO  - Inflamm Res. 2022 Jun;71(5-6):577-590. doi: 10.1007/s00011-022-01565-3. Epub 2022 
      Apr 12.