Retinal Astrocytes and GABAergic Wide-Field Amacrine Cells Express PDGFRα: Connection to Retinal Ganglion Cell Neuroprotection by PDGF-AA

Author(s): Takahama S (1), Adetunji MO (1), Zhao T (2), Chen S2, Li W (2), Tomarev SI (1)

1 Section on Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Institutes of Health, Bethesda, Maryland, United States.
2 Retinal Neurophysiology Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.

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 PDGFRα-enhanced green fluorescent protein (EGFP) mice to identify retinal cells that may be essential for RGC protection by PDGF-AA.

METHODS: PDGFRα-EGFP mice expressing nuclear-targeted EGFP under the control of the PDGFRα promoter were used. Localization of PDGFRα 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, PDGFRα 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 PDGFRα, whereas RGCs (in vivo or in vitro) did not. PDGFRα-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.

Invest Ophthalmol Vis Sci. 2017 Sep 1;58(11):4703-4711. doi: 10.1167/iovs.21783.

PMID: 28910446

http://www.ncbi.nlm.nih.gov/pubmed/28910446

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