E Levinger1, E Zemel2, I Perlman3. 1. Department of Ophthalmology, Tel Aviv Medical Center, Tel Aviv, Israel. 2. Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and the Rappaport Institute, P.O.Box 9649, 31096, Haifa, Israel. 3. 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.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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. CONCLUSION: 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.
Authors: Stephanie Niklaus; Lucia Cadetti; Colette M Vom Berg-Maurer; André Lehnherr; Adriana L Hotz; Ian C Forster; Matthias Gesemann; Stephan C F Neuhauss Journal: eNeuro Date: 2017-06-12
Authors: Andreas Bringmann; Antje Grosche; Thomas Pannicke; Andreas Reichenbach Journal: Front Endocrinol (Lausanne) Date: 2013-04-17 Impact factor: 5.555