Oxidative stress causes ERK phosphorylation and cell death in cultured retinal pigment epithelium: prevention of cell death by AG126 and 15-deoxy-delta 12, 14-PGJ2

  • BMC Ophthalmol. 2003 Mar 21;3:5. doi: 10.1186/1471-2415-3-5.
Tarun K Garg  1 ,  Jason Y Chang
Affiliations
  • 1. Departments of Anatomy & Neurobiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. [email protected]
PMID: 12659653 DOI: 10.1186/1471-2415-3-5
Abstract

Background: The retina, which is exposed to both sunlight and very high levels of oxygen, is exceptionally rich in polyunsaturated fatty acids, which makes it a favorable environment for the generation of Reactive Oxygen Species. The cytotoxic effects of hydrogen peroxide (H2O2) induced oxidative stress on retinal pigment epithelium were characterized in this study.

Methods: The MTT cell viability assay, Texas-Red phalloidin staining, immunohistochemistry and Western blot analysis were used to assess the effects of oxidative stress on primary human retinal pigment epithelial cell cultures and the ARPE-19 cell line.

Results: The treatment of retinal pigment epithelial cells with H2O2 caused a dose-dependent decrease of cellular viability, which was preceded by a significant cytoskeletal rearrangement, activation of the Extracellular signal-Regulated Kinase, lipid peroxidation and nuclear condensation. This cell death was prevented partially by the prostaglandin derivative, 15d-PGJ2 and by the protein kinase inhibitor, AG126.

Conclusion: 15d-PGJ2 and AG126 may be useful pharmacological tools in the future capable of preventing oxidative stress induced RPE cell death in human ocular diseases.

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