Platelet-Derived Growth Factor Receptor Alpha Is Associated with Oxidative Stress-Induced Retinal Cell Death

Abstract

The purpose of this study was to investigate the role played by platelet-derived growth factor-α (PDGFRα) in oxidative stress-induced retinal cell death. A previous proteomic study from our laboratory showed that expression of PDGFRα is elevated considerably in the retinas of an animal model of glaucoma-the excitatory amino acid carrier (EAAC) 1-deficient (EAAC1-/-) mouse. Retinal sites and expression patterns of PDGFRα were determined by immunohistochemistry in the retinas of EAAC1-/- and control CRL:CD1(ICR) mice. A retinal cell line was exposed to hydrogen peroxide, and expression PDGFRα determined by Western blot analysis. Effects of PDGF-AA and PDGFRα-siRNA on hydrogen peroxide-induced retinal cell death were examined. PDGFRα was detected in the retinal ganglion cell layer (RGL) of both EAAC1-/- and ICR mice, and was also localized in the internal nuclear layer (INL) of EAAC1-/- mice. While treatment with excess PDGF-AA had no additional effect on retinal cell death, expression of PDGFRα increased with exposure to hydrogen peroxide. Hydrogen peroxide-induced retinal cell death was inhibited by exposure to PDGF-AA via phosphatidylinositol 3 kinase (PI3K); cell death was promoted by PDGFRα-siRNA. PDGFRα is expressed in mouse retina, where it is essential for retinal cell survival under conditions of oxidative stress.