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Human retinal epithelium produces and responds to placenta growth factor

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Abstract

Background

Placenta growth factor (PlGF) is an important co-factor in retinal neovascularization. To examine whether retinal pigment epithelial (RPE) cells may represent a source for PlGF during retinopathy, we determined whether human RPE cells in vitro produce and respond to PlGF. In addition, we determined whether the cells express receptors for PlGF, i.e. flt-1 and neuropilins.

Methods

Cultured human RPE cells of passages 3–5 were used. The regulation of the PlGF gene and protein expression by growth factors and cytokines was evaluated by quantitative PCR and ELISA. Proliferation rates and chemotaxis were determined by a bromodeoxyuridine and a Boyden chamber assay.

Results

Human RPE cells express mRNAs for various members of the vascular endothelial growth factor family and for their receptors, including mRNAs for PlGF, flt-1, KDR, and neuropilins-1 and -2. The expression levels of the mRNAs for neuropilins-1 and -2 were significantly higher than those for flt-1 and KDR. Members of the transforming growth factor (TGF)-β superfamily of growth factors (BMP-4, TGF-β1, and β2) were strong inducers of PlGF gene expression, and evoked secretion of PlGF-2 protein by RPE cells. Exogenous PlGF-2 induced chemotaxis in RPE cells and reduced slightly the cell proliferation at high concentrations.

Conclusion

The findings that RPE cells produce and respond to PlGF indicate that the factor exerts an autocrine/paracrine action on these cells. It is suggested that increased expression of TGF-β-related growth factors during diabetic retinopathy may cause PlGF secretion by RPE cells contributing to the stimulation of cell migration as a critical component of the progression of fibrovascular membranes.

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Abbreviations

bFGF:

basic fibroblast growth factor

BMP:

bone morphogenetic protein

BrdU:

bromodeoxyuridine

ERK:

extracellular signal-regulated kinase

flt:

FMS-related tyrosine kinase1 (VEGF-R1)

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

HB-EGF:

heparin-binding epridermal growth factor-like growth factor

HGF:

hepatocyte growth factor

IL:

interleukin

KDR:

kinase insert domain receptor (VEGF-R2)

MAPK:

mitogen-activated protein kinase

PCR:

polymerase chain reaction

PDGF:

platelet-derived growth factor

PI3K:

phosphatidylinositol-3 kinase

PlGF:

placenta growth factor

RPE:

retinal pigment epithelium

TGF:

transforming growth factor

TNF:

tumor necrosis factor

VEGF:

vascular endothelial growth factor

VEGF-R:

VEGF receptor

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Acknowledgements

The authors thank Ute Weinbrecht for excellent technical assistance. This work was supported by grants from the Deutsche Forschungsgemeinschaft (KO 1547/4-1; BR 1249/2-1).

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Authors and Affiliations

  1. Department of Ophthalmology, Eye Clinic, University of Leipzig Medical Faculty, Liebigstrasse 10–14, 04103, Leipzig, Germany

    Margrit Hollborn, Solveig Tenckhoff, Marlen Seifert, Stephanie Köhler, Peter Wiedemann, Andreas Bringmann & Leon Kohen

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  1. Margrit Hollborn
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  2. Solveig Tenckhoff
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Correspondence to Margrit Hollborn.

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Hollborn, M., Tenckhoff, S., Seifert, M. et al. Human retinal epithelium produces and responds to placenta growth factor. Graefe's Arch Clin Exp Ophthalmo 244, 732–741 (2006). https://doi.org/10.1007/s00417-005-0154-9

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  • DOI: https://doi.org/10.1007/s00417-005-0154-9

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