Abstract
Abstract: :
Purpose: To determine whether human retinal pigment epithelial (RPE) cells express and respond to placenta growth factor (PlGF). Methods: Cultures of human RPE cells were evaluated for mRNA expression of members of the vascular endothelial growth factor (VEGF) family of growth factors and of their receptors by RT–PCR. The regulation of PlGF gene and protein expression by various growth factors and cytokines was determined by qRT–PCR and ELISA. Proliferation rates were determined by a bromodeoxyuridine immunoassay, and chemotaxis was investigated by a Boyden chamber assay. Results: Human RPE cells express mRNAs for various members of the VEGF family of growth factors and for their receptors, including mRNAs for VEGF–A, –B, –C, –D, PlGF–2, Flt–1, KDR, and neuropilins–1 and –2. The expression levels of the mRNAs for neuropilins–1 and –2 were higher when compared to the mRNAs for Flt–1 and KDR. Exogenous PlGF enhanced the expression of neuropilin–1. The Members of the transforming growth factor (TGF)–ß superfamily, BMP–4, TGF–ß1 and TGF–ß2 are strong inducers of the PlGF gene expression, and evoke secretion of PlGF protein by RPE cells. Various growth factors and pro–inflammatory cytokines did not influence the expression of PlGF. Exogenous PlGF–2 induces chemotaxis in RPE cells and reduces slightly the cell proliferation at high concentrations. Conclusions: The finding that RPE cells secrete and respond to PlGF suggests that the factor exerts an autocrine/paracrine action on these cells. Increased retinal expression of TGF–ß–related growth factors during proliferative retinopathies may cause facilitation of PlGF expression by RPE cells that may contribute to the stimulation of cell migration as a critical component of the progression of epiretinal membranes.
Keywords: retinal pigment epithelium • cytokines/chemokines • proliferative vitreoretinopathy