Diabetes-induced dysfunction of the glutamate transporter in retinal Müller cells.
OBJECTIVE
A decrease in the ability of Müller cells to remove glutamate from the extracellular space may play a critical role in the disruption of glutamate homeostasis that occurs in the diabetic retina. Because this amino acid is toxic to retinal neurons and is likely to exacerbate oxidative stress, elucidation of the mechanisms by which glutamate levels are elevated in diabetes may help in the understanding of the pathogenesis of diabetic retinopathy. This study tested the hypothesis that the function of the glutamate transporter in Müller cells of the diabetic retina is compromised by a mechanism involving oxidation.


METHODS
Müller cells were freshly isolated from normal rats and those made diabetic by streptozotocin injection. The activity of the Müller cell glutamate transporter, which is electrogenic, was monitored by the perforated-patch configuration of the patch-clamp technique.


RESULTS
Four weeks after the onset of hyperglycemia, a significant dysfunction of the Müller cell glutamate transporter was detected. After 13 weeks of streptozotocin-induced diabetes, the activity of this transporter was decreased by 67%. Consistent with oxidation's causing this dysfunction, exposure to a disulfide-reducing agent rapidly restored the activity of the glutamate transporter in Müller cells of diabetic retinas.


CONCLUSIONS
Early in the course of diabetic retinopathy, the function of the glutamate transporter in Müller cells is decreased by a mechanism that is likely to involve oxidation.
Li
Qing
Q
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, USA.
Puro
Donald G
DG
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004594:Electrophysiology; D018698:Glutamic Acid / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009457:Neuroglia / Q000378:metabolism*; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000378:metabolism*
D027322:Amino Acid Transport System X-AG; D018698:Glutamic Acid