PMID- 15985430
OWN - NLM
STAT- MEDLINE
DCOM- 20051025
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 35
DP  - 2005 Sep 2
TI  - Involvement of inflammation, degradation, and apoptosis in a mouse model of 
      glaucoma.
PG  - 31240-8
AB  - Glaucoma is a common cause of blindness affecting at least 66 million people 
      worldwide. Pigmentary glaucoma is one of the most common forms of secondary 
      glaucoma, and its pathogenesis remains unclear. Interleukin-18 (IL-18) is an 
      important regulator of innate and acquired immune responses and plays an 
      important role in inflammatory/autoimmunity diseases. Using the DBA/2J mouse as 
      an animal model of human pigmentary glaucoma, we demonstrated for the first time 
      that the expression of the IL-18 protein and gene in the iris/ciliary body and 
      level of IL-18 protein in the aqueous humor of DBA/2J mice are dramatically 
      increased with age. This increase precedes the onset of clinical evidence of 
      pigmentary glaucoma, implying a pathogenic role of inflammation/immunity in this 
      disease. We also observed that activated NF-kappaB and phosphorylated MAPK are 
      increased in the iris/ciliary body of DBA/2J mice, suggesting that both signaling 
      pathways may be involved in IL-18 mediated pathogenesis of pigmentary glaucoma in 
      the eyes of DBA/2J mice. In addition, matrix metalloproteinase-2 (MMP-2) 
      expression in the iris/ciliary body and the activity of MMP-2 in the aqueous 
      humor are increased whereas tissue inhibitor of matrix metalloproteinase-1 
      (TIMP-1) expression in the iris/ciliary body is decreased, indicating that the 
      degradation process is involved in this mouse model of pigmentary glaucoma. 
      Furthermore, the expressions of apoptosis-related genes, caspase-8, Fas, FADD, 
      FAP, and FAF, and the activity of caspase-3 are increased in the iris/ciliary 
      body of DBA/2J mice. Elucidation of biochemical and molecular mechanisms of IL-18 
      participation in the pathogenesis of pigmentary glaucoma should provide 
      approaches for developing improved and targeted treatments to ameliorate this 
      blinding disease. The possibility that altered IL-18 expression in the eye of 
      DBA/2J mice initiates and/or amplifies the pathogenesis of pigmentary glaucoma 
      requires further investigation.
FAU - Zhou, Xiaohong
AU  - Zhou X
AD  - Department of Ophthalmology, Dean A. McGee Eye Institute, University of Oklahoma 
      Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
FAU - Li, Feng
AU  - Li F
FAU - Kong, Li
AU  - Kong L
FAU - Tomita, Hiroshi
AU  - Tomita H
FAU - Li, Chao
AU  - Li C
FAU - Cao, Wei
AU  - Cao W
LA  - eng
GR  - EY014427/EY/NEI NIH HHS/United States
GR  - EY12190/EY/NEI NIH HHS/United States
GR  - P20 RR17703/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050628
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, T-Lymphocyte)
RN  - 0 (CD69 antigen)
RN  - 0 (Interleukin-18)
RN  - 0 (Lectins, C-Type)
RN  - 0 (NF-kappa B)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Aging/physiology
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Antigens, Differentiation, T-Lymphocyte/metabolism
MH  - Apoptosis/physiology
MH  - Ciliary Body/anatomy & histology/immunology/pathology
MH  - *Disease Models, Animal
MH  - Gene Expression Regulation
MH  - Glaucoma, Open-Angle/*immunology/*pathology/physiopathology
MH  - Humans
MH  - Interleukin-18/*immunology
MH  - Intraocular Pressure
MH  - Iris/cytology/immunology/pathology
MH  - Lectins, C-Type
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Retinal Ganglion Cells/cytology/metabolism/pathology
MH  - Signal Transduction/physiology
MH  - T-Lymphocytes/immunology
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics/metabolism
EDAT- 2005/06/30 09:00
MHDA- 2005/10/26 09:00
CRDT- 2005/06/30 09:00
PHST- 2005/06/30 09:00 [pubmed]
PHST- 2005/10/26 09:00 [medline]
PHST- 2005/06/30 09:00 [entrez]
AID - S0021-9258(20)79401-9 [pii]
AID - 10.1074/jbc.M502641200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Sep 2;280(35):31240-8. doi: 10.1074/jbc.M502641200. Epub 2005 
      Jun 28.