Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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 %).
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.
This PDF is available to Subscribers Only