Expression of tissue inhibitor of metalloproteinase-4 in normal human corneal cells and experimental corneal neovascularization.
OBJECTIVE
To study the expression of TIMP-4 in cultured corneal cells and in corneal neovascularization.


METHODS
Human limbo-corneal epithelial cells, fibroblasts, and endothelial cells were cultured in serum-free, PMA- or basic fibroblast growth factor (bFGF)-treated condition. Neovascularization in rat cornea was induced by suturing. The expression of TIMP-4 was examined by immunohistochemistry, Western blot and RT-PCR.


RESULTS
TIMP-4 was constitutively expressed in cultured human corneal cells. The expression was only mildly enhanced after mitogen treatment. TIMP-4 immunoreactivity was predominantly expressed in normal rat corneal epithelium, and also in ingrowing blood vessels following suturing, which persisted up to day 28. Increased staining in corneal epithelium and blood vessels were also noted in vascularized human corneas.


CONCLUSIONS
TIMP-4 is expressed in the cornea, which may play a role in modulating extracellular matrix remodeling associated with corneal wound healing and angiogenesis.
Ma
David Hui-Kang
DH
Department of Ophthalmology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan. davidhkma@yahoo.com
Zhang
Fen
F
Shi
Wen
W
Yao
Jeng-Yuan
JY
Hsiao
Ching-Hsi
CH
Wu
Hui-Chuan
HC
Kim
Wan-Soo
WS
Hao
Yan-Xia
YX
Hwang
David G
DG
Chen
Jan-Kan
JK
Tsai
Ray Jui-Fang
RJ
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D016510:Corneal Neovascularization / Q000378:metabolism*; D003319:Corneal Stroma / Q000166:cytology / Q000378:metabolism*; D004195:Disease Models, Animal; D004728:Endothelium, Corneal / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D019573:Epithelium, Corneal / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D007124:Immunoenzyme Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D000097792:Tissue Inhibitor of Metalloproteinase-4
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4