The effects of excitatory amino acids and their transporters on function and structure of the distal retina in albino rabbits

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) followup 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.