PMID- 24515951
OWN - NLM
STAT- MEDLINE
DCOM- 20140721
LR  - 20211021
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 229
IP  - 8
DP  - 2014 Aug
TI  - Interleukin-18 has antipermeablity and antiangiogenic activities in the eye: 
      reciprocal suppression with VEGF.
PG  - 974-83
LID - 10.1002/jcp.24575 [doi]
AB  - Interleukin-18 (IL-18) is increased along with IL-1beta by activation of the 
      inflammasome and has been implicated in inflammatory and autoimmune diseases, but 
      its role in the eye is uncertain. In patients with macular edema due to retinal 
      vein occlusion, intraocular IL-18 levels increased significantly (P < 0.001) 
      after treatment with ranibizumab particularly in patients with high baseline 
      IL-18 which correlated with good visual outcome (P < 0.05). In mice with ischemic 
      retinopathy, suppression of VEGF caused an increase in IL18 mRNA due to an 
      increase in IL-18-positive myeloid cells. VEGF significantly and specifically 
      inhibited IL-18 production by myeloid cells stimulated with lipopolysaccharide 
      (P < 0.001). Intraocular injection of IL-18 reduced VEGF-induced leakage and 
      neovascularization, and reversed VEGF-induced suppression of Claudin5 expression 
      and Claudin 5 labeling of vascular tight junctions. Injection of IL-18 also 
      increased expression of Thrombospondin 1 and reduced ischemia-induced retinal 
      neovascularization relevant to diabetic retinopathy and subretinal 
      neovascularization relevant to neovascular age-related macular degeneration. 
      Thus, VEGF and IL-18 suppress each other's production and effects on the 
      vasculature suggesting that IL-18 may provide benefit in multiple 
      retinal/choroidal vascular diseases.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Shen, Jikui
AU  - Shen J
AD  - Department of Ophthalmology, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland; Department of Neuroscience, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland.
FAU - Choy, David F
AU  - Choy DF
FAU - Yoshida, Tsunehiko
AU  - Yoshida T
FAU - Iwase, Takeshi
AU  - Iwase T
FAU - Hafiz, Gulnar
AU  - Hafiz G
FAU - Xie, Bing
AU  - Xie B
FAU - Hackett, Sean F
AU  - Hackett SF
FAU - Arron, Joseph R
AU  - Arron JR
FAU - Campochiaro, Peter A
AU  - Campochiaro PA
LA  - eng
GR  - R01 EY005951/EY/NEI NIH HHS/United States
GR  - R01 EY012609/EY/NEI NIH HHS/United States
GR  - EY012609/EY/NEI NIH HHS/United States
PT  - Editorial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Claudin-5)
RN  - 0 (Cldn5 protein, mouse)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-18)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - ZL1R02VT79 (Ranibizumab)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal, Humanized/pharmacology
MH  - Claudin-5/genetics/metabolism
MH  - Cytokines/genetics/metabolism
MH  - Eye/*blood supply/*metabolism
MH  - Gene Expression Regulation/physiology
MH  - Interleukin-18/genetics/*metabolism
MH  - Mice
MH  - Neovascularization, Pathologic/genetics/*metabolism
MH  - Permeability
MH  - Ranibizumab
MH  - Retinal Vessels/physiology
MH  - Tight Junctions/physiology
MH  - Vascular Endothelial Growth Factor A/genetics/*metabolism
PMC - PMC4364659
MID - NIHMS668271
EDAT- 2014/02/12 06:00
MHDA- 2014/07/22 06:00
PMCR- 2015/08/01
CRDT- 2014/02/12 06:00
PHST- 2013/12/05 00:00 [received]
PHST- 2014/02/06 00:00 [accepted]
PHST- 2014/02/12 06:00 [entrez]
PHST- 2014/02/12 06:00 [pubmed]
PHST- 2014/07/22 06:00 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - 10.1002/jcp.24575 [doi]
PST - ppublish
SO  - J Cell Physiol. 2014 Aug;229(8):974-83. doi: 10.1002/jcp.24575.