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Abstract #12578 Published in IGR 7-3
Neurochemical evidence to implicate elevated glutamate in the mechanisms of high intraocular pressure (IOP)-induced retinal ganglion cell death in rat
Nucci C; Tartaglione R; Rombola L; Morrone LA; Fazzi E; Bagetta GNeurotoxicology 2005; 26: 935-941
See also comment(s) by Manuel Vidal-Sanz • William Hare • Leonard A. Levin •
High intraocular pressure (IOP)-induced ischemia is a model for retinal neurodegeneration that recapitulates pathological features almost identical to those seen in patients after central retinal or ophthalmic artery occlusion and may also represent a model of acute angle closure glaucoma. Using this experimental model, we present data indicating that acute IOP elevation for 45 min is followed by a progressive decline in the number of retinal ganglion cells (RGC) which appear to die via an apoptotic mechanism. The observation that systemic treatment with MK801, a N-methyl-d-aspartate (NMDA) receptor antagonist, with GYKI52466, a non-NMDA receptor antagonist, or with l-NAME, an inhibitor of nitric oxide synthase (NOS), prevents the RGC loss observed 24 after IOP elevation strongly suggests an excitotoxic, glutamate-mediated, mechanism of RGC death. The latter deduction is strengthened by the evidence that a microdialysis probe placed into the retinal tissue of rats bearing IOP elevation revealed an increase (90% as compared to baseline value) in glutamate levels that peaked 130 min after the beginning of reperfusion and was reversed by a pre-treatment with MK801. Collectively, our data suggest that acute elevation of IOP increases intraretinal levels of glutamate with consequent abnormal activation of NMDA and non-NMDA subtypes of glutamate receptors and increased NOS activity leading to excitotoxic, glutamate-mediated, RGC death.
Dr. C. Nucci, Physiopathological Optics, Department of Biopathology, University of Rome Tor Vergata, Rome, Italy. nucci@med.uniroma2.it
Classification:
5 Experimental glaucoma; animal models
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
3.7 Biochemistry (Part of: 3 Laboratory methods)
1.3 Pathogenesis (Part of: 1 General aspects)
