Abstract
Purpose: :
Previous studies show that the epidermal growth factor receptor (EGFR) is present in neurons of both developing and adult central nervous system (CNS). During the development of the CNS, EGFR regulates neuronal migration, proliferation and differentiation. However, the localization and functions of EGFR in adult neurons are not well defined. To test possible physiological roles of EGFR in neurons, we have investigated the localization of EGFR and its ligands in the normal adult rat, mouse and human retina.
Methods: :
We used immunohistochemistry and immunoblot to identify the localization of EGFR and its ligands in the normal adult rat, mouse and human retina and in the rat ganglion cell line, RGC–5. Using RGC–5 cells, we investigated changes in cell morphology and neurofilaments in response to an EGFR ligand, EGF (100 ng/ml).
Results: :
EGFR was present in the retinal ganglion cells of all three species and in displaced amacrine cells in the rat. EGFR was also present in the inner nuclear layer (INL) and outer plexiform layer (OPL) of the rat retina, the INL of the mouse retina and the INL and outer nuclear layer (ONL) of the human retina. The EGFR ligands, epidermal growth factor (EGF), transforming growth factor–α (TGF–α), amphiregulin, and heparin–binding epidermal growth factor–like growth factor (HB–EGF), were also present in the ganglion cell layer of all three species. In other retinal layers, these ligands had different distribution patterns. In response to EGF, RGC–5 cells became elongated with fewer but much longer and thinner processes. EGF also induced hyperphosphorylation of neurofilament–H in the RGC–5 cells. Hyperphosphorylation was blocked by AG1478, a specific EGFR tyrosine kinase inhibitor.
Conclusions: :
EGFR and its ligands are present in retinal ganglion cells and several other neurons of the normal, adult rat, mouse and human retina. Activation of EGFR on the soma of retinal ganglion cells may modulate physiological activities of certain neurofilaments in retinal ganglion cell axons.
Keywords: growth factors/growth factor receptors • retina • ganglion cells