The effects of excitatory amino acids and their transporters on function and structure of the distal retina in albino rabbits.
OBJECTIVE
To study the physiological and pathological roles of excitatory amino acid transporters in the distal retina of albino rabbits.


METHODS
Albino rabbits were injected intravitreally in one eye with different doses of L- or D-isomers of glutamate or aspartate, with mixtures of L-glutamate and antagonists to glutamate receptors or with inhibitors of glutamate transporters. The other eye was injected with saline, and served as a control. The electroretinogram (ERG) was recorded 4 h and 2 weeks after injection. At the end of the ERG follow-up period, retinas were prepared for light microscopy.


RESULTS
The ERG b-wave was reduced and the a-wave augmented by both isomers of EAAs when tested 4 h after injection. Long-term (2-week) follow-up indicated severe damage to the retina by both isomers of EAAs. Antagonists to glutamate-gated ionic channels failed to protect the rabbit distal retina from permanent damage. Competitive inhibitors of GLAST-1 transporter were highly effective in blocking synaptic transmission in the OPL and in inducing permanent ERG deficit. Selective inhibition of the GLT-1 transporter caused short-term augmentation of the ERG and no permanent ERG deficit.


CONCLUSIONS
GLAST-1, the glutamate transporter of Müller cells, plays a major role in synaptic transmission within the OPL of the rabbit retina. Over-activation of GLAST-1 seems to induce permanent damage to the distal rabbit retina via yet unidentified mechanism.
Department of Ophthalmology, Tel Aviv Medical Center, Tel Aviv, Israel.
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E
Levinger
Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and the Rappaport Institute, P.O.Box 9649, 31096, Haifa, Israel.
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E
Zemel
Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and the Rappaport Institute, P.O.Box 9649, 31096, Haifa, Israel. iperlman@technion.ac.il.
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Perlman
D027322:Amino Acid Transport System X-AG / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology*; D004596:Electroretinography / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D027341:Excitatory Amino Acid Transporter 1 / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology*; D058449:Intravitreal Injections; D011817:Rabbits; D012160:Retina / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D027322:Amino Acid Transport System X-AG; D018691:Excitatory Amino Acid Antagonists; D027341:Excitatory Amino Acid Transporter 1; C493393:Slc1a3 protein, mouse; D001224:Aspartic Acid; D018698:Glutamic Acid