Modification of glutamine synthetase expression by mammalian Müller (glial) cells in retinal organ cultures

Abstract

One of the key enzymes in glial-neuronal transmitter recycling is glutamine synthetase (GS). In the retina, GS is exclusively expressed by glial (Müller) cells where it serves to convert neuron-released active transmitter substances (glutamate and GABA) into glutamine. Experiments on avian retinae have shown that GS expression is developmentally regulated by glucocorticoid hormones and, to a lesser extent, by a non-hormonal control mechanism(s). Much less is known about GS regulation in mammalian retinae, although either increases or decreases of GS immunoreactivity have been observed in Müller cells in different forms of retinal pathologies. We studied GS expression in postnatal rabbit retinae both in vivo and explanted as wholemounts in vitro, using immunocytochemistry and Western immunoblotting. GS expression was detectable in vivo from the fourth postnatal day, and increased rapidly within the first weeks of life. Levels were lower in vitro than in vivo by an order of magnitude, and could be significantly stimulated (> 60-110%) in vitro by application of hydrocortisone, conditioned medium from cultured retinal pigment epithelium and glutamate or ammonia, but not GABA. It is concluded that GS expression in mammalian Müller cells is dependent on systemic control by glucocorticoid hormones, as observed in birds, but environmental (activity-dependent) factors may play a more important role in mammals.