Coincidence of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) immunoreactions in retinal glia: evidence for coupling of GLAST and GS in transmitter clearance.
Our aim was to identify proteins that mediate the uptake and degradation of synaptically released glutamate, focusing on the rat retina with its well-defined glutamatergic pathways. Immunoreactivity against the L-glutamate/L-aspartate transporter (GLAST) is present in Müller cells. Ultrastructurally, even the finest glial processes, particularly those ensheathing identified structures of glutamatergic transmission (rod spherules), are immunoreactive for GLAST. Further light and electron microscopic observations revealed that also retinal astrocytes and pigment epithelial cells are immunoreactive for GLAST. No neuronal or microglial staining was observed. This is in line with uptake of exogenous [3H]glutamate previously localized specifically in Müller cells and pigment epithelium (Ehinger and Falck: Brain Res 33:157-172, 1971). Since endogenous glutamate can only be demonstrated in Müller cells if glutamine synthetase (GS) is inhibited (Pow and Robinson: Neuroscience 60:355-366, 1994), the immunocytochemical localization of GS was determined. GS immunoreactivity was found in all but only those cell types immunoreactive for GLAST. The light and electron microscopic patterns of immunoreactivity were very similar, particularly in the outer plexiform layer. The three cell types containing both GS and GLAST (Müller cells, astrocytes, and retinal pigment epithelium) are related developmentally. In the light of the two references quoted the present data indicate that the proteins mediating retinal uptake and degradation of synaptically released glutamate may be GLAST and GS, respectively, and that they may operate in concert to terminate the neurotransmitter action of glutamate.
Institute of Anatomy, J.W. Goethe University, Frankfurt/M., Germany.
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D027322:Amino Acid Transport System X-AG; D000818:Animals; D001253:Astrocytes / Q000276:immunology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000276:immunology*; D005260:Female; D005973:Glutamine / Q000096:biosynthesis* / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D008297:Male; D009434:Neural Pathways; D009457:Neuroglia / Q000276:immunology* / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D006023:Glycoproteins; D005973:Glutamine