Retinal Astrocytes And Gabaergic Wide-Field Amacrine Cells Express Pdgfr Alpha: Connection To Retinal Ganglion Cell Neuroprotection By Pdgf-Aa

PURPOSE. Our previous experiments demonstrated that intravitreal injection of platelet-derived growth factor-AA (PDGF-AA) provides retinal ganglion cell (RGC) neuroprotection in a rodent model of glaucoma. Here we used PDGFRa-enhanced green fluorescent protein (EGFP) mice to identify retinal cells that may be essential for RGC protection by PDGF-AA.METHODS. PDGFR alpha-EGFP mice expressing nuclear-targeted EGFP under the control of the PDGFR alpha promoter were used. Localization of PDGFR alpha in the neural retina was investigated by confocal imaging of EGFP fluorescence and immunofluorescent labeling with a panel of antibodies recognizing different retinal cell types. Primary cultures of mouse RGCs were produced by immunopanning. Neurobiotin injection of amacrine cells in a flat-mounted retina was used for the identification of EGFP-positive amacrine cells in the inner nuclear layer.RESULTS. In the mouse neural retina, PDGFR alpha was preferentially localized in the ganglion cell and inner nuclear layers. Immunostaining of the retina demonstrated that astrocytes in the ganglion cell layer and a subpopulation of amacrine cells in the inner nuclear layer express PDGFR alpha, whereas RGCs (in vivo or in vitro) did not. PDGFR alpha-positive amacrine cells are likely to be Type 45 gamma-aminobutyric acidergic (GABAergic) wide-field amacrine cells.CONCLUSIONS. These data indicate that the neuroprotective effect of PDGF-AA in a rodent model of glaucoma could be mediated by astrocytes and/or a subpopulation of amacrine cells. We suggest that after intravitreal injection of PDGF-AA, these cells secrete factors protecting RGCs.