PMID- 30658033
OWN - NLM
STAT- MEDLINE
DCOM- 20190510
LR  - 20190510
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 59
IP  - 13
DP  - 2018 Nov 1
TI  - Sleep Deprivation Induces Dry Eye Through Inhibition of PPARalpha Expression in 
      Corneal Epithelium.
PG  - 5494-5508
LID - 10.1167/iovs.18-24504 [doi]
AB  - PURPOSE: To determine if sleep deprivation induces dry eye through altering 
      peroxisome proliferator-activated receptor alpha (PPARalpha) expression in mice. 
      METHODS: The "stick over water" sleep deprivation-induced dry eye (SDE) model 
      evaluated PPARalpha involvement in inducing this condition. Scanning electron 
      microscopy (SEM) examined microvilli morphology in superficial corneal epithelial 
      cells (SCECs) in SDE and PPARalpha-/- mice. Quantitative RT-PCR (qRT-PCR) and Western 
      blot (WB) or immunostaining evaluated PPARalpha, carnitine palmitoyl transferase 1alpha 
      (CPT1alpha), and transient receptor potential vanilloid 6 (TRPV6) expression levels 
      and Ezrin phosphorylation status. Hematoxylin-eosin and Oil Red O staining 
      characterized meibomian gland morphology and corneal lipid accumulation, 
      respectively. Phenol red cotton threads measured tear production. In cultured 
      corneal epithelial sheets, qRT-PCR, WB, and SEM determined the individual effects 
      of fenofibrate and MK886 (PPARalpha agonist and antagonist, respectively) on PPARalpha, 
      TRPV6 expression, and SCEC microvilli morphology. RESULTS: Corneal epithelial 
      lipid accumulation, microvilli morphologic changes, and decreased tear production 
      were associated with marked declines in PPARalpha, CPT1alpha, and TRPV6 expression levels 
      as well as Ezrin phosphorylation status, whereas meibomian glands were unaltered 
      in SDE mice. These effects of SDE mice mimicked those in their nonstressed 
      PPARalpha-/-counterpart. Topical application of fenofibrate reversed these effects in 
      SDE corneas. In cultured corneal epithelial sheets, fenofibrate increased PPARalpha 
      and TRPV6 gene and protein expression levels and restored microvilli morphology, 
      whereas MK886 attenuated these changes. CONCLUSIONS: Sleep deprivation induces 
      dry eye through abnormal SCEC microvilli morphology, which is caused by 
      sequential downregulation of PPARalpha, TRPV6 expression, and Ezrin phosphorylation 
      status in mice.
FAU - Tang, Liying
AU  - Tang L
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Wang, Xue
AU  - Wang X
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Wu, Jieli
AU  - Wu J
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Li, San Ming
AU  - Li SM
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Zhang, Zhaoqiang
AU  - Zhang Z
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Wu, Sangang
AU  - Wu S
AD  - Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated 
      Hospital of Xiamen University, Xiamen, Fujian, China.
FAU - Su, Ting
AU  - Su T
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Lin, Zhirong
AU  - Lin Z
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
AD  - Xiamen University Affiliated Xiamen Eye Center, Xiamen, Fujian, China.
FAU - Chen, Xueting
AU  - Chen X
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Liao, Xulin
AU  - Liao X
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Bai, Ting
AU  - Bai T
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Qiu, Yan
AU  - Qiu Y
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Reinach, Peter Sol
AU  - Reinach PS
AD  - Wenzhou Medical University, Wenzhou, Zhejiang, China.
FAU - Li, Wei
AU  - Li W
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
AD  - Xiamen University Affiliated Xiamen Eye Center, Xiamen, Fujian, China.
AD  - The Affiliated Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China.
FAU - Chen, Yongxiong
AU  - Chen Y
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
FAU - Liu, Zuguo
AU  - Liu Z
AD  - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of 
      Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, 
      Fujian, China.
AD  - Xiamen University Affiliated Xiamen Eye Center, Xiamen, Fujian, China.
AD  - The Affiliated Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Calcium Channels)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (Indoles)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 0 (PPAR alpha)
RN  - 0 (Ppara protein, mouse)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (Trpv6 protein, mouse)
RN  - 0 (ezrin)
RN  - 080626SQ8C (MK-886)
RN  - EC 2.3.1.21 (CPT1B protein, mouse)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - U202363UOS (Fenofibrate)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Calcium Channels/genetics/metabolism
MH  - Carnitine O-Palmitoyltransferase/genetics/metabolism
MH  - Cells, Cultured
MH  - Cytoskeletal Proteins/metabolism
MH  - Disease Models, Animal
MH  - Dry Eye Syndromes/*etiology/metabolism
MH  - Epithelium, Corneal/drug effects/*metabolism
MH  - Fenofibrate/pharmacology
MH  - Hypolipidemic Agents/pharmacology
MH  - Indoles/pharmacology
MH  - Lipoxygenase Inhibitors/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microscopy, Electron, Scanning
MH  - PPAR alpha/*antagonists & inhibitors/metabolism
MH  - Phosphorylation
MH  - Real-Time Polymerase Chain Reaction
MH  - Sleep Deprivation/*complications/metabolism
MH  - TRPV Cation Channels/genetics/metabolism
MH  - Tears/physiology
EDAT- 2019/01/19 06:00
MHDA- 2019/05/11 06:00
CRDT- 2019/01/19 06:00
PHST- 2019/01/19 06:00 [entrez]
PHST- 2019/01/19 06:00 [pubmed]
PHST- 2019/05/11 06:00 [medline]
AID - 2716365 [pii]
AID - 10.1167/iovs.18-24504 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2018 Nov 1;59(13):5494-5508. doi: 
      10.1167/iovs.18-24504.