The activation of MEK-ERK1/2 by glutamate receptor-stimulation is involved in the regulation of RPE proliferation and morphologic transformation

Reyna Lizette Pacheco-Domínguez, J. Prisco Palma-Nicolas, Edith López, Ana María López-Colomé

Research output: Contribution to journalArticle

Abstract

Retinal pigment epithelial (RPE) cells are the main cell type involved in the pathogenesis of proliferative vitreoretinopathy (PVR). As a result from retinal detachment or surgical procedures, RPE comes in contact with glutamate from serum, glial release and the injured retina. The purpose of this study was to explore a possible role for glutamate in the development of PVR, mediated by the receptor-stimulated activation of the ERK1/2 MAPK pathway, the alteration of cell proliferation and the transdifferentiation of RPE cells, using rat RPE cells in culture as a model system. We demonstrated the expression in these cells of Group I metabotropic-and ionotropic AMPA/KA and NMDA glutamate receptors (GluRs), predominantly of the NMDA subtype, which are targeted to the membrane, and exhibit pharmacological and biochemical characteristics equivalent to those previously established in brain tissue. Proliferation was measured by MTS-reduction colorimetric assay, and actin cytoskeleton dynamics was visualized by immunoflurescence using α-sma specific antibodies. Activation of metabotropic, AMPA and NMDA receptors by glutamate induced the time-and dose-dependent phosphorylation of ERK1/2,assessed by Western blot analysis, in parallel to a significant increase in cell proliferation and a decrease in α-sma expression and its recruitment into stress fibers. These effects were all prevented by the inhibition of MEK. Hence, results suggest that glutamate could be involved in the generation of PVR, through a GluR-mediated increase in proliferation and phenotypic transformation, cause-effect related to the activation of ERK1/2.

Original languageEnglish (US)
Pages (from-to)207-219
Number of pages13
JournalExperimental eye research
Volume86
Issue number2
DOIs
Publication statusPublished - Feb 1 2008
Externally publishedYes

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Keywords

  • actin cytoskeleton
  • glutamate
  • MAP kinases
  • proliferation, epithelio-mesenchymal transition

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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