gms | German Medical Science

102. Jahrestagung der DOG

Deutsche Ophthalmologische Gesellschaft e. V.

23. bis 26.09.2004, Berlin

Inhibition of mesenchymal transdifferentiation of RPE cells by hepatocyte growth factor: a new aspect in the pathogenesis of PVR

Meeting Abstract

  • corresponding author M.-A. Gamulescu - University Eye Clinic, Regensburg; Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, USA
  • M. Jin - Doheny Eye Institut, Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, USA
  • S. He - Doheny Eye Institut, Department of Ophthalmology and Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, USA
  • C. Spee - Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, USA
  • V.-P. Gabel - University Eye Clinic, Regensburg
  • S. Ryan - Doheny Eye Institut, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, USA
  • D. R. Hinton - Doheny Eye Institut, Department of Ophthalmology and Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, USA

Evidenzbasierte Medizin - Anspruch und Wirklichkeit. 102. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft. Berlin, 23.-26.09.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04dogP 132

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dog2004/04dog623.shtml

Veröffentlicht: 22. September 2004

© 2004 Gamulescu et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

The pathophysiology of proliferative vitreoretinopathy (PVR) after intraocular surgery is not yet completely understood. Still, the transdifferentiation of retinal pigment epithelial cells (RPE) from their normal epithelial to a mesenchymal phenotype seems to be an important step herein. In vitro transdifferentiated cells (e.g. after treatment with transforming growth factor beta (TGFβ)) show an increased expression of smooth muscle actin (SMA) and a more fibroblast-like morphology. Also, increased levels of TGFβ2 were found in the vitreous of PVR-eyes. Hepatocyte growth factor (HGF) on the other hand is an anti-fibrotic und proliferation-promoting factor. In this study we investigated, whether HGF can inhibit a TGFβ-induced transdifferentiation of RPE-cells.

Methods

Subconfluent human RPE cells were grown primarily in DMEM with 10% fetal bovine serum (FBS). At the beginning of treatment, the percentage of serum was reduced to 1%, in order to promote a pure cytokine reaktion of the cells. Human recombinant TGFβ2 (5ng/ml) and human recombinant HGF in different concentrations (2,5; 5; 10; 20; 40ng/ml) were added to the cultures for three days. As a marker for transdifferentiation, SMA-expression of the cells was measured using flow cytometry, real-time polymerase chain reaction and western blotting.

Results

The daily treatment with HGF (20 und 40ng/ml) reduced the TGFβ2-induced increase in SMA-expression in a dose-dependent manner, as assessed by all methods. Although downregulation of SMA did not reach control levels even with the highest HGF concentration (40ng/ml), it was statistically significant.

Conclusions

Those results may lead to a better understanding of the interaction between RPE-cells, cytokines and extracellular matrix in the context of mesenchymal transdifferentiation and of possible modulating mechanisms of PVR in vivo.