Latanoprost stimulates secretion of matrix metalloproteinases in tenon fibroblasts both in vitro and in vivo.
OBJECTIVE
To investigate the presence and the possible role of different matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in Tenon capsule fibroblasts. These enzymes are essential for the control of tissue remodeling in the context of wound repair. This aspect is important to further the understanding of and possibly to influence the scarring process of filtering blebs after glaucoma surgery.


METHODS
Untreated and latanoprost-treated human Tenon fibroblasts were examined for the presence of MMPs and TIMPs on the mRNA and protein levels. Assays performed included RT-PCR, real-time RT-PCR, immunocytochemistry, Western blot analysis, flow cytometry, and zymography. To investigate the changes in vivo, conjunctival specimens of rabbits treated with latanoprost eye drops were examined by immunohistochemistry.


RESULTS
In all assays, both MMP-3 and TIMP-2 were detected. With the real-time RT-PCR technique, MMP-1, -2, -3, -7, -9, and -14 and TIMP-1 and -2 were detected. An upregulation of MMP-3 and TIMP-2 after latanoprost treatment of the fibroblasts was shown and found to occur on the mRNA and the protein levels. The upregulation of MMP-3 and TIMP-2 was confirmed in vivo.


CONCLUSIONS
Tenon fibroblasts contain the ability on the mRNA level to synthesize all enzymes of the MMP and TIMP family that are related to remodeling of the extracellular matrix. The levels of MMP-3 and TIMP-2 increase after treatment with latanoprost. Tenon fibroblasts may be the target cells for attempts to influence the tissue levels of MMPs and TIMPs in the context of conjunctival wound healing after glaucoma surgery.
Mietz
Holger
H
Department of Ophthalmology, University of Cologne, 50924 Koeln, Germany. h.mietz@uni-koeln.de
Esser
Johannes M
JM
Welsandt
Gerhard
G
Kociok
Norbert
N
Hueber
Arno
A
Joussen
Antonia
A
Esser
Peter
P
Krieglstein
Günter K
GK
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D003228:Conjunctiva / Q000187:drug effects* / Q000378:metabolism; D005205:Fascia / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D000077338:Latanoprost; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D000077338:Latanoprost; D020782:Matrix Metalloproteinases