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-Daspartate (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 IOPelevation 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 pretreatment 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.

Neurochemical evidence to implicate elevated glutamate in the mechanisms of high intraocular pressure (IOP)-induced retinal ganglion cell death in rat

ROMBOLA', Laura;MORRONE, Luigi Antonio;BAGETTA, Giacinto
2005

Abstract

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-Daspartate (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 IOPelevation 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 pretreatment 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11770/144849
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