Alkylphosphocholines: a new therapeutic option in glaucoma filtration surgery.
OBJECTIVE
To investigate the effect of alkylphosphocholines (APCs) on human Tenon fibroblast (HTF) proliferation, migration, and cell-mediated collagen gel contraction.


METHODS
HTFs were isolated from tissue samples of three patients obtained during surgery and cultured in DMEM and 10% fetal calf serum (FCS). HTFs (passage 3-6) were treated with one APC in different concentrations spanning the 50% inhibitory concentration (IC(50)), as determined previously. Inhibition of cell proliferation was assessed by the tetrazolium dye reduction assay. Migration was determined in chemoattractant chambers with fibronectin-coated polycarbonated membranes. For inhibition of contraction, three-dimensional collagen gels were seeded with HTFs, and the gel size was measured. Cell viability was determined by the trypan blue exclusion assay. For analysis of the mechanism of action, protein kinase C (PKC) activity was measured.


RESULTS
The IC(50) varied between 7.0 and 10.5 microM for all APCs tested. At this concentration, all four APCs inhibited HTF migration and cell-mediated collagen gel contraction in the presence of serum. The inhibitory effects on HTF proliferation, migration, and contraction were observed at nontoxic concentrations. PKC activity was reduced to 50% of control level at the IC(50) of all APCs applied.


CONCLUSIONS
APCs are effective inhibitors of HTF proliferation, migration, and cell-mediated contraction of collagen gels at nontoxic concentrations. Their mechanism of action seems to involve the inhibition of the PKC pathway.
Departments of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
Kirsten H
KH
Eibl
Bernhard
B
Banas
Daniel
D
Kook
Anne V
AV
Ohlmann
Siegfried
S
Priglinger
Anselm
A
Kampik
Ulrich C
UC
Welge-Luessen
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology; D005355:Fibrosis / Q000517:prevention & control; D018463:Filtering Surgery; D005901:Glaucoma / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D010767:Phosphorylcholine; D003094:Collagen; D011493:Protein Kinase C