PMID- 25121097
OWN - NLM
STAT- MEDLINE
DCOM- 20150902
LR  - 20211021
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2014
DP  - 2014
TI  - Caspase-14 expression impairs retinal pigment epithelium barrier function: 
      potential role in diabetic macular edema.
PG  - 417986
LID - 10.1155/2014/417986 [doi]
LID - 417986
AB  - We recently showed that caspase-14 is a novel molecule in retina with potential 
      role in accelerated vascular cell death during diabetic retinopathy (DR). Here, 
      we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells 
      (RPE) dysfunction under hyperglycemia. The impact of high glucose (HG, 30 mM 
      D-glucose) on caspase-14 expression in human RPE (ARPE-19) cells was tested, 
      which showed significant increase in caspase-14 expression compared with normal 
      glucose (5 mM D-glucose + 25 mM L-glucose). We also evaluated the impact of 
      modulating caspase-14 expression on RPE cells barrier function, phagocytosis, and 
      activation of other caspases using ARPE-19 cells transfected with caspase-14 
      plasmid or caspase-14 siRNA. We used FITC-dextran flux assay and electric cell 
      substrate impedance sensing (ECIS) to test the changes in RPE cell barrier 
      function. Similar to HG, caspase-14 expression in ARPE-19 cells increased 
      FITC-dextran leakage through the confluent monolayer and decreased the 
      transcellular electrical resistance (TER). These effects of HG were prevented by 
      caspase-14 knockdown. Furthermore, caspase-14 knockdown prevented the HG-induced 
      activation of caspase-1 and caspase-9, the only activated caspases by HG. 
      Phagocytic activity was unaffected by caspase-14 expression. Our results suggest 
      that caspase-14 contributes to RPE cell barrier disruption under hyperglycemic 
      conditions and thus plays a role in the development of diabetic macular edema.
FAU - Beasley, Selina
AU  - Beasley S
AUID- ORCID: 0000-0001-6728-6400
AD  - Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents 
      University (GRU), Augusta, GA 30912, USA ; Oral Biology/Anatomy, College of 
      Dental Medicine, GRU, Augusta, GA 30912, USA ; Culver Vision Discovery Institute 
      and Department of Ophthalmology, Medical College of Georgia, GRU, Augusta, GA 
      30912, USA.
FAU - El-Sherbiny, Mohamed
AU  - El-Sherbiny M
AUID- ORCID: 0000-0002-2689-1409
AD  - Oral Biology/Anatomy, College of Dental Medicine, GRU, Augusta, GA 30912, USA ; 
      Culver Vision Discovery Institute and Department of Ophthalmology, Medical 
      College of Georgia, GRU, Augusta, GA 30912, USA ; Department of Anatomy, Mansoura 
      Faculty of Medicine, Mansoura University, Mansoura, Egypt.
FAU - Megyerdi, Sylvia
AU  - Megyerdi S
AD  - Oral Biology/Anatomy, College of Dental Medicine, GRU, Augusta, GA 30912, USA ; 
      Culver Vision Discovery Institute and Department of Ophthalmology, Medical 
      College of Georgia, GRU, Augusta, GA 30912, USA.
FAU - El-Shafey, Sally
AU  - El-Shafey S
AD  - Oral Biology/Anatomy, College of Dental Medicine, GRU, Augusta, GA 30912, USA.
FAU - Choksi, Karishma
AU  - Choksi K
AD  - Oral Biology/Anatomy, College of Dental Medicine, GRU, Augusta, GA 30912, USA.
FAU - Kaddour-Djebbar, Ismail
AU  - Kaddour-Djebbar I
AD  - Department of Physiology, Medical College of Georgia, GRU and Charlie Norwood VA 
      Medical Center, Augusta, GA 30912, USA.
FAU - Sheibani, Nader
AU  - Sheibani N
AD  - Departments of Ophthalmology and Visual Sciences and Biomedical Engineering, 
      University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, 
      USA.
FAU - Hsu, Stephen
AU  - Hsu S
AD  - Oral Biology/Anatomy, College of Dental Medicine, GRU, Augusta, GA 30912, USA.
FAU - Al-Shabrawey, Mohamed
AU  - Al-Shabrawey M
AUID- ORCID: 0000-0001-5362-7972
AD  - Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents 
      University (GRU), Augusta, GA 30912, USA ; Oral Biology/Anatomy, College of 
      Dental Medicine, GRU, Augusta, GA 30912, USA ; Culver Vision Discovery Institute 
      and Department of Ophthalmology, Medical College of Georgia, GRU, Augusta, GA 
      30912, USA ; Department of Anatomy, Mansoura Faculty of Medicine, Mansoura 
      University, Mansoura, Egypt.
LA  - eng
GR  - P30 CA014520/CA/NCI NIH HHS/United States
GR  - R01 EY023315/EY/NEI NIH HHS/United States
GR  - R24 EY022883/EY/NEI NIH HHS/United States
GR  - 5R01 EY023315-02/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140709
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 (Dextrans)
RN  - 0 (fluorescein isothiocyanate dextran)
RN  - EC 3.4.22.- (Caspase 14)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Caspase 14/*metabolism
MH  - Cell Line
MH  - Dextrans/metabolism
MH  - Diabetic Retinopathy/*enzymology/pathology
MH  - Fluorescein-5-isothiocyanate/analogs & derivatives/metabolism
MH  - Fluorescent Antibody Technique
MH  - Gene Knockdown Techniques
MH  - Glucose/pharmacology
MH  - Humans
MH  - Macular Edema/*enzymology/pathology
MH  - Models, Biological
MH  - Permeability/drug effects
MH  - Phagocytosis/drug effects
MH  - Retinal Pigment Epithelium/drug effects/*enzymology/*pathology
PMC - PMC4119899
EDAT- 2014/08/15 06:00
MHDA- 2015/09/04 06:00
PMCR- 2014/07/09
CRDT- 2014/08/15 06:00
PHST- 2014/05/01 00:00 [received]
PHST- 2014/06/06 00:00 [accepted]
PHST- 2014/08/15 06:00 [entrez]
PHST- 2014/08/15 06:00 [pubmed]
PHST- 2015/09/04 06:00 [medline]
PHST- 2014/07/09 00:00 [pmc-release]
AID - 10.1155/2014/417986 [doi]
PST - ppublish
SO  - Biomed Res Int. 2014;2014:417986. doi: 10.1155/2014/417986. Epub 2014 Jul 9.