April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
The Glutamate Transporter Inhibitor, DL-Threo-Beta-Benzyloxyaspartate (DL-TBOA), Prevents Neurochemical Effects but Not Neurotoxicity Yielded in the Retina by Elevated Intraocular Pressure (IOP)-Induced Ischemia/Reperfusion in Rat
Author Affiliations & Notes
  • R. Russo
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
  • F. Cavaliere
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
  • G. P. Varano
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
  • G. Bagetta
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
    Sect. Neuropharmacol. Norm. Pathol. Neur. Plasticity, Cosenza, Italy
  • M. Corasaniti
    Pharmacobiol. Science, University Magna Graecia, Catanzaro, Italy
  • L. A. Morrone
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
    Sect. Neuropharmacol. Norm. Pathol. Neur. Plasticity, Cosenza, Italy
  • Footnotes
    Commercial Relationships  R. Russo, None; F. Cavaliere, None; G.P. Varano, None; G. Bagetta, None; M. Corasaniti, None; L.A. Morrone, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2249. doi:
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      R. Russo, F. Cavaliere, G. P. Varano, G. Bagetta, M. Corasaniti, L. A. Morrone; The Glutamate Transporter Inhibitor, DL-Threo-Beta-Benzyloxyaspartate (DL-TBOA), Prevents Neurochemical Effects but Not Neurotoxicity Yielded in the Retina by Elevated Intraocular Pressure (IOP)-Induced Ischemia/Reperfusion in Rat. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2249.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Introduction: : Ischemic phenomena are common features of retinal pathological conditions, including glaucoma, anterior ischemic optic neuropathy and retinal vessels occlusion (see Osborne et al., 2004, Eye 18:1075-1084). Several studies suggest that excitotoxicity occurs during retinal ischemia leading to retinal ganglion cells (RGCs) death.

Purpose: : Using a model of retinal ischemia induced by transient elevation of IOP we investigated on the role of excitatory amino acid transporters (EAATs) in the extracellular changes of glutamate (GLU) in the vitreous.

Methods: : Retinal ischemia was induced in the eye of adult Wistar rats by acutely increasing the IOP. Extracellular GLU was monitored in the vitreous before, during and after pressure-induced ischemia using a microdialysis technique (Nucci et al., 2005, Neurotoxicology, 26: 935-941). DL-TBOA or coenzyme Q10 (CoQ10) were administered intravitreally. RGCs labeling by intracollicular injection of FluoroGold was used for evaluation of cellular survival.

Results: : Extracellular level of GLU increased by 70% in the first 10 min of ischemia with a larger and significant (P<0.05 vs pre-ischemia) increase during reperfusion. Administration of DL-TBOA (500 µM) minimized the accumulation of GLU, though it worsened the delayed RGCs loss typically observed under these conditions (DL-TBOA 50 ±10.5 vs control 25.9± 4.2 %; n= 3). Importantly, pre-ischemic treatment with the free radical scavenger CoQ10 reduced extracellular GLU raise (86% reduction vs control) seen during reperfusion and prevented RGCs loss (CoQ10 12±3.8 vs control 25.9± 4.2 %).

Conclusions: : Our data suggest that derangement of the mechanisms underlying glutamate transport is a key event triggering excitotoxicity in the ischemic retina and provide useful pharmacologic information for the correct use of DL-TBOA as a tool to study ischemia/reperfusion mechanisms in in vivo settings.

Keywords: excitatory neurotransmitters • ischemia • retina 
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