Are neuronal transporters relevant in retinal glutamate homeostasis?

Exposure of isolated retinas to 30 mu M D-aspartate, which is a substrate f or all high affinity glutamate transporters, for 30 min, resulted in the ac cumulation of such D-aspartate into Muller glial cells but not glutamatergi c neurons as evinced by immunocytochemistry for D-aspartate. Further incuba tion of such loaded retinas in physiological media, in the absence of D-asp artate, resulted in the slow release of accumulated D-aspartate from the Mu ller cells and its accumulation into populations of photoreceptors and bipo lar cells. This result indicates that after initial transport into Muller c ells, reversal of direction of transport of D-aspartate, and thus by infere nce glutamate, by GLAST, readily occurs. D-aspartate released by Muller cel ls was strongly accumulated into cone photoreceptors which are known to exp ress GLT-1, and into rod photoreceptors which we demonstrate here to expres s the retina specific glutamate transporter EAAT5 (excitatory amino transpo rter 5). Populations of glutamatergic bipolar cells, which express GLT-1 al so exhibited avid uptake of D-aspartate. We conclude that the Muller cell g lutamate transporter GLAST is responsible for most of the initial glutamate clearance in the retina after its release from neurones. However, some glu tamate is also returned from Muller cells, to neurons expressing GLT-1 and EAATS, albeit at a slow rate. These data suggest that the role of neuronal glutamate transporters in the retina may be to facilitate a slow process of recycling glutamate back from Muller cells to neurons after its initial cl earance from perisynaptic regions by GLAST. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.