Abstract

DO.16.07

Growth factor inhibitors for pharmacological wound modulation after filtrating glaucoma surgery: the human tenon’s capsule fibroblast as an in vitro example

Hager T., Metzner S., Knop E., Rieck P.
Department of Ophthalmology, Charité Medical Faculty, Campus Virchow Hospital, Humboldt University Berlin, Berlin

Objective: The goal of postoperative care after trabeculectomy shifts increasingly from a pure suppression of proliferation of human tenon’s capsule fibroblasts to an inhibition of all functions controlled by these cells including proliferation, migration, extracellular matrix production and transformation to myofibroblasts. The regulation of these functions is achieved by a concerted action of numerous growth factors. We analyzed the impact of growth factor inhibitors such as Suramin and Genistein on tenon fibroblasts in vitro and contrasted the results to the already established antimetabolite 5-FU.
Methods: Primary cultures of tenon fibroblasts were used. The migration behaviour after addition of the drugs was tested in a transwell assay system. The examination of proliferation behaviour of a defined cell number was studied with a cell count method. The fibronectin content of supernatants was analyzed at several time points with an ELISA. The determination of the transformation rate from tenon fibroblasts tomyofibroblasts after addition of the drugs was carried out on the basis of a double fluorescence staining.
Results: All drugs applied were able to inhibit the migration of tenon fibroblasts as well as their transformation to myofibroblasts. However, a complete suppression of these functions was not achieved. Suramin inhibited the proliferation only slightly. In contrast, the proliferation level of genistein and 5-FU was in the range of the initial values at all times of assessment. All tested drugs diminished the expression of fibronectin by 50 %.
Conclusions: Both Genistein and Suramin are capable of inhibiting the functions of the human tenon fibroblast significantly. Genistein has a stronger effect in specified cell functions than the well-established 5-FU. Suramin has a weaker effect on fibroblast-functions than 5-FU.

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