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Graefe's Archive for Clinical and Experimental Ophthalmology
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 11/2014

01-11-2014 | Basic Science

Hyperthermia-induced upregulation of vascular endothelial growth factor in retinal pigment epithelial cells is regulated by mitogen-activated protein kinases

Authors: Hendrik Faby, Jost Hillenkamp, Johann Roider, Alexa Klettner

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 11/2014

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Abstract

Purpose

Localized application of hyperthermia is a potential treatment for retinal diseases. Vascular endothelial growth factor (VEGF) derived from the retinal pigment epithelium (RPE) is implicated in a variety of retinal pathologies. As it has been recently shown that hyperthermia may induce VEGF in the RPE, the aim of this study was to investigate hyperthermia-induced VEGF secretion and the pathways of hyperthermal VEGF upregulation in the RPE.

Material and methods

The human RPE cell line (Arpe-19) was exposed to 40°, 42°, 45° and 50 °C for one, five and 15 min. Cell viability was evaluated using a trypan blue exclusion assay, VEGF secretion was evaluated by an enzyme-linked immunosorbent assay ELISA) and VEGF expression was investigated using a Western blot. Involvement of mitogen-activated protein kinase (MAPK) pathways (ERK1/2, JNK, p38) and transient receptor potential vanilloid (TRPV) channels on VEGF induction was investigated using commercially available inhibitors (U0126, SB203580, SP600125, ruthenium red). Expression and phosphorylation of MAPKs was investigated using a Western blot.

Results

Hyperthermia induces time- and temperature-dependent cell death in human RPE cells. VEGF expression and secretion is induced by hyperthermia in a time- and temperature-dependent manner mediated by p38 and to a lesser degree by JNK. TRPV channels seem to play a minor role in regulation of hyperthermia-induced VEGF secretion.

Conclusions

Hyperthermia induces temperature-dependent secretion of VEGF in the RPE, which is mediated by p38 and, to a lesser extent, JNK. This may lead to undesired effects from hyperthermal treatment of retinal diseases.
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Metadata
Title
Hyperthermia-induced upregulation of vascular endothelial growth factor in retinal pigment epithelial cells is regulated by mitogen-activated protein kinases
Authors
Hendrik Faby
Jost Hillenkamp
Johann Roider
Alexa Klettner
Publication date
01-11-2014
Publisher
Springer Berlin Heidelberg
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 11/2014
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-014-2750-z

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