High Intraocular Pressure (IOP)-Induced Ischemia Elevates Extracellular Glutamate in the Retina of Rat: Pharmacological Evidence to Implicate Derangement of Glutamate Transporters

Abstract

Purpose: : to study by ocular microdialysis the extracellular changes of glutamate in high IOP-induced ischemia in vivo, in the presence of DL-threo-beta-benzyloxyaspartate (DL-TBOA), a non selective, non-transportable blocker of excitatory amino acid transporters (EAATs) or a solution (coenzyme Q10 (0.1%) and Vitamin E (0.5%) (CoQun, Visufarma, Italy)) with documented free-radical scavenger and anti-apoptotic properties (Nucci et al., 2007 Int. Rev. Neurobiol.).

Methods: : retinal ischemia was induced in the right eye of anaesthetised, male, Wistar rat (250 g) by acutely increasing the IOP (see Osborne et al., 2004, Prog Ret Eye Res) and extracellular glutamate monitored during and after ischemia using microdialysis (see Nucci et al., 2005, Neurotoxicology). DL-TBOA or Coenzyme Q10 + Vitamin E solution were administered intravitreally via the microdialysis probe.

Results: : extracellular glutamate increases during the first 10 min of ischemia though this reach statistical significace 10 min and 150 min after the reperfusion had started. Administration of DL-TBOA (500 µM) during ischemia showed a trend towards glutamate increase at 10 min after reperfusion and a more sustained glutamate increase after 150 min of reperfusion without reaching, however, statistical significance whereas Coenzyme Q10 + Vitamin E solution ablated the peak increases typically induced by ischemia-reperfusion sequence.

Keywords: neuroprotection • excitatory neurotransmitters • oxidation/oxidative or free radical damage