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Antifibrotic effects of tocotrienols on human Tenon's fibroblasts

Tappeiner, Christoph and Meyenberg, Alexander and Goldblum, David and Mojon, Daniel and Zingg, Jean-Marc and Nesaretnam, Kalanithi and Kilchenmann, Monika and Frueh, Beatrice E.. (2010) Antifibrotic effects of tocotrienols on human Tenon's fibroblasts. Graefe's archive for clinical and experimental ophthalmology, Vol. 248, Nr. 1. pp. 65-71.

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Official URL: http://edoc.unibas.ch/dok/A6003133

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Abstract

PURPOSE: To compare the antifibrotic effect of vitamin E isoforms alpha-, gamma-, and delta-tocotrienol on human Tenon's fibroblasts (hTf) to the antimetabolite mitomycin C. METHODS: Antifibrotic effects of alpha- (40, 60, 80, 100, and 120 muM), gamma- (10, 20, 30, and 40 muM) and delta-tocotrienol (10, 20, 30, and 40 muM) on hTf cultures were evaluated by performing proliferation, migration and collagen synthesis assays. Whereas for vitamin E the exposure time was set to 7 days to mimic subconjunctival application, cultures were exposed only 5 min to mitomycin C 100 mug/ml to mimic intraoperative administration. Cell morphology (phase contrast microscopy) as an assessment for cytotoxicity and cell density by measuring DNA content in a fluorometric assay to determine proliferation inhibition was performed on day 0, 4, and 7. Migration ability and collagen synthesis of fibroblasts were measured. RESULTS: All tested tocotrienol isoforms were able to significantly inhibit hTf proliferation in a dose-dependent manner (maximal inhibitory effect without relevant morphological changes at day 4 for alpha-tocotrienol 80 muM with 36.7% and at day 7 for alpha-tocotrienol 80 muM with 42.6% compared to control). Degenerative cell changes were observed in cultures with concentrations above 80 muM for alpha- and above 30 muM for gamma- and delta-tocotrienol. The highest collagen synthesis inhibition has been found with 80 microM alpha-tocotrienol (62.4%) and no significant inhibition for mitomycin C (2.5%). Migration ability was significantly reduced in cultures exposed to 80 microM alpha- and 30 microM gamma-tocotrienol (inhibition of 82.2% and 79.5%, respectively, compared to control) and also after mitomycin C treatment (60.0%). Complete growth inhibition without significant degenerative cell changes could only be achieved with mitomycin C. CONCLUSION: In vitro, all tested tocotrienol isoforms were able to inhibit proliferation, migration and collagen synthesis of human Tenon's fibroblasts and therefore may have the potential as an anti-scarring agent in filtrating glaucoma surgery.
Faculties and Departments:03 Faculty of Medicine > Bereich Spezialfächer (Klinik) > Ehemalige Einheiten Spezialfächer (Klinik) > Ophthalmologie (Flammer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Spezialfächer (Klinik) > Ehemalige Einheiten Spezialfächer (Klinik) > Ophthalmologie (Flammer)
UniBasel Contributors:Goldblum, David
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Springer
ISSN:0721-832X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Jan 2013 08:37
Deposited On:04 Jan 2013 08:34

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