Abstract
Purpose: 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.
Methods: 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.
Results: 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.
Conclusions: PDGFRα is expressed in mouse retina, where it is essential for retinal cell survival under conditions of oxidative stress.
ACKNOWLEDGMENTS
The authors wish to thank Prof. Neeraj Agawal for providing the RGC-5 cells and Prof. Duco Hamasaki for kindly helping to edit the manuscript. Also appreciated is the editorial assistance of Dr. Kathryn Pokorny.
Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.