Abstract

P 110

Different effects of PDGF and TGF-beta on fibroblast contractility and cell morphology

Tobias Meyer-ter-Vehn, Hong Han
Universitäts-Augenklinik Würzburg

Objective
Postoperative scarring is the most common cause of secondary failure in filtering glaucoma surgery. During woundhealing various cytokines impact this process by influence the behaviour of fibroblasts.
Aim of the presented study is to investigate the effect of two cytokines involved in this process, Platelet Derived Growth Factor (PDGF) and Transforming Growth Factor beta (TGF-beta), on fibroblasts regarding transdifferentiation to myofibroblasts, contractility and cellular morphology.
Methods
Human tenon fibroblasts were treated with TGF-beta or PDGF. Myofibroblastic transdifferentiation was assessed by expression of the marker smooth muscle actin (SMA) using RealTime PCR and Westernblot. Contractility and three dimensional cell morphology were addressed by fibroblast populated collagen gels contraction assays with consecutive laser scanning microscopy.
Results
Both TGF-beta and PDGF stimulated gel contraction. TGF-beta caused a robust expression of SMA and activation of SMAD and p38 signalling cascade. PDGF instead induced only a faint SMA expression and no activation of SMAD or p38 signalling cascade. On the structural site TGF-beta induced a bipolar cell morphology with intracellular stress fibers whereas PDGF lead to increased development of dentritic protrusions, suggestive for increased migratory activity.
Conclusions
While stimulation with PDGF induced a dentritic morphology compatible with increased migratory activity, TGF-beta caused myofibroblastic transdifferentiation. Both are central aspects of conjunctival woundhealing. A better understanding of the effects of the various cytokines involved in this process potentially provides new concepts for a specific antifibrotic therapy.

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