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Nigel Louis Barnett, David Vaughan Pow; Antisense Knockdown of GLAST, a Glial Glutamate Transporter, Compromises Retinal Function. Invest. Ophthalmol. Vis. Sci. 2000;41(2):585-591.
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purpose. To elucidate the role of the glial glutamate transporter GLAST, in the
regulation of retinal function.
methods. Antisense oligonucleotides to GLAST were injected intravitreally into
the left eye of Wistar rats. Sense oligonucleotides (control) were
injected into the right eye over a period of 3 days. Scotopic flash
electroretinograms were recorded over a 20-day period. To assay whether
the antisense oligonucleotides caused a reduction in the expression or
the activity of GLAST, retinas were exposed to d-aspartate,
a nonendogenous substrate of glutamate transporters. The retinas were
immunolabeled with specific antibodies for d-aspartate.
Retinal GLAST and glutamate distributions also were determined
results. Antisense oligonucleotides markedly suppressed the electroretinogram
b-wave, whereas sense oligonucleotides had no significant effect.
Significant changes in the electroretinogram were apparent 5 days after
injection of antisense oligonucleotide and were sustained for at least
20 days. A marked reduction of d-aspartate uptake into
Müller cells of retinas that had been exposed to the antisense
oligonucleotides 5 days previously suggests a reduction of GLAST
activity. The retinas, however, displayed no evidence of excitotoxic
neuronal degeneration, and the distribution of glutamate was unaffected
by antisense treatment.
conclusions. The observed lack of neuronal degeneration suggests that reduced
glutamate uptake into Müller cells does not cause excitotoxic
tissue damage. A direct perturbation of glutamatergic signaling is more
likely, because the rapid clearance of glutamate is necessary for light
elicited signaling between photoreceptors and bipolar cells. This
suggests that GLAST is essential for the maintenance of normal retinal
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