PMID- 30973208
OWN - NLM
STAT- MEDLINE
DCOM- 20200731
LR  - 20210109
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 23
IP  - 6
DP  - 2019 Jun
TI  - The role of autophagy in the pathogenesis of exposure keratitis.
PG  - 4217-4228
LID - 10.1111/jcmm.14310 [doi]
AB  - Incomplete tear film spreading and eyelid closure can cause defective renewal of 
      the ocular surface and air exposure-induced epithelial keratopathy (EK). In this 
      study, we characterized the role of autophagy in mediating the ocular surface 
      changes leading to EK. Human corneal epithelial cells (HCECs) and C57BL/6 mice 
      were employed as EK models, respectively. Transmission electron microscopy (TEM) 
      evaluated changes in HCECs after air exposure. Each of these models was treated 
      with either an autophagy inhibitor [chloroquine (CQ) or 3-methyladenine (3-MA)] 
      or activator [Rapamycin (Rapa)]. Immunohistochemistry assessed autophagy-related 
      proteins, LC3 and p62 expression levels. Western blotting confirmed the 
      expression levels of the autophagy-related proteins [Beclin1 and mammalian target 
      of rapamycin (mTOR)], the endoplasmic reticulum (ER) stress-related proteins 
      (PERK, eIF2alpha and CHOP) and the PI3K/Akt/mTOR signalling pathway-related proteins. 
      Real-time quantitative PCR (qRT-PCR) determined IL-1beta, IL-6 and MMP9 gene 
      expression levels. The TUNEL assay detected apoptotic cells. TEM identified 
      autophagic vacuoles in both EK models. Increased LC3 puncta formation and 
      decreased p62 immunofluorescent staining and Western blotting confirmed autophagy 
      induction. CQ treatment increased TUNEL positive staining in HCECs, while Rapa 
      had an opposite effect. Similarly, CQ injection enhanced air exposure-induced 
      apoptosis and inflammation in the mouse corneal epithelium, which was inhibited 
      by Rapa treatment. Furthermore, the phosphorylation status of PERK and eIF2alpha and 
      CHOP expression increased in both EK models indicating that ER stress-induced 
      autophagy promoted cell survival. Taken together, air exposure-induced autophagy 
      is indispensable for the maintenance of corneal epithelial physiology and cell 
      survival.
CI  - (c) 2019 The Authors. Journal of Cellular and Molecular Medicine published by John 
      Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
FAU - Wang, Guoliang
AU  - Wang G
AD  - Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen 
      University, Xiamen, China.
AD  - Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, 
      China.
FAU - Xue, Yuhua
AU  - Xue Y
AD  - School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.
FAU - Wang, Yanzi
AU  - Wang Y
AD  - Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen 
      University, Xiamen, China.
AD  - Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, 
      China.
FAU - Dong, Fei
AU  - Dong F
AD  - Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen 
      University, Xiamen, China.
AD  - Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, 
      China.
FAU - Shen, Mei
AU  - Shen M
AD  - Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen 
      University, Xiamen, China.
AD  - Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, 
      China.
FAU - Zong, Rongrong
AU  - Zong R
AD  - Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen 
      University, Xiamen, China.
AD  - Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, 
      China.
FAU - Liu, Zuguo
AU  - Liu Z
AD  - Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen 
      University, Xiamen, China.
AD  - Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, 
      China.
FAU - Li, Cheng
AU  - Li C
AUID- ORCID: 0000-0002-0449-3709
AD  - Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen 
      University, Xiamen, China.
AD  - Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190411
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 886U3H6UFF (Chloroquine)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Autophagy/drug effects/*physiology
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Chloroquine/pharmacology
MH  - Endoplasmic Reticulum/drug effects/metabolism/pathology
MH  - Endoplasmic Reticulum Stress/drug effects/physiology
MH  - Eukaryotic Initiation Factor-2/metabolism
MH  - Female
MH  - Humans
MH  - Keratitis/drug therapy/metabolism/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microtubule-Associated Proteins/metabolism
MH  - Phosphorylation/drug effects/physiology
MH  - Signal Transduction/drug effects/physiology
MH  - Transcription Factor CHOP/metabolism
PMC - PMC6533494
OTO - NOTNLM
OT  - air exposure
OT  - autophagy
OT  - corneal epithelium
OT  - endoplasmic reticulum stress
OT  - exposure keratopathy
COIS- The authors declare that there is no conflict of interest.
EDAT- 2019/04/12 06:00
MHDA- 2020/08/01 06:00
PMCR- 2019/06/01
CRDT- 2019/04/12 06:00
PHST- 2018/11/18 00:00 [received]
PHST- 2019/03/03 00:00 [revised]
PHST- 2019/03/08 00:00 [accepted]
PHST- 2019/04/12 06:00 [pubmed]
PHST- 2020/08/01 06:00 [medline]
PHST- 2019/04/12 06:00 [entrez]
PHST- 2019/06/01 00:00 [pmc-release]
AID - JCMM14310 [pii]
AID - 10.1111/jcmm.14310 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2019 Jun;23(6):4217-4228. doi: 10.1111/jcmm.14310. Epub 2019 Apr 
      11.