Increased glutamate levels in the vitreous of patients with retinal detachment * Roselie M.H. Diederen a, * , Ellen C. La Heij a , Nicolaas E.P. Deutz b , Aize Kijlstra a , Alfons G.H. Kessels c , Hans M.H. van Eijk b , Albert T.A. Liem a , Suzanne Dieudonne ´ a , Fred Hendrikse a a Department of Ophthalmology, University Hospital Maastricht, 6202 AZ, Maastricht, The Netherlands b Department of Surgery, University of Maastricht, The Netherlands c Department of Clinical Epidemiology and Medical Technology Assessment, University Hospital Maastricht, The Netherlands Received 13 February 2005; accepted in revised form 22 October 2005 Available online 10 March 2006 Abstract Experimental models have implicated glutamate in the irreversible damage to retinal cells following retinal detachment. In this retrospective study we investigated a possible role for glutamate and other amino acid neurotransmitters during clinical rhegmatogenous retinal detachment (RRD). Undiluted vitreous samples were obtained from 176 patients undergoing pars plana vitrectomy. The study group consisted of 114 pa- tients (114 eyes) with a rhegmatogenous retinal detachment. Controls included 52 eyes with an idiopathic macular hole or idiopathic epiretinal membrane and 10 eyes with a traction retinal detachment due to proliferative diabetic retinopathy. Vitreous concentrations of glutamate, gamma- aminobutyric acid (GABA), taurine, glycine, and aspartate were determined by high-pressure liquid chromatography (HPLC). Multivariate anal- ysis was used to examine a possible association between amino acid neurotransmitter levels and several clinical variables including visual acuity. The mean vitreous concentration of glutamate in eyes with a rhegmatogenous retinal detachment (16.6  5.6 mM) was significantly higher as compared to the controls (13.1  5.2 mM) (P ¼ 0.001). Taurine levels were also increased in RRD, whereas no significant difference could be observed in glycine, aspartate and GABA levels when comparing RRD with controls. A correlation was found between increased vitreous glutamate and a lower pre-operative visual acuity. No association was, however, observed between post-operativevisual acuity and the level of any of the five amino acid neurotransmitters. RRD was associated with a significantly increased vitreous glutamate concentration. Using visual acuity as a functional parameter in this study, we could not demonstrate a correlation between vitreous glutamate, or any of the other tested amino acid neurotransmitters and visual outcome. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: retinal detachment; glutamate; excitotoxicity; amino acid; vitreous 1. Introduction Glutamate is an excitatory neurotransmitter in the retina, which after its release from neurons is cleared from the extracellular environment via uptake by Mu ¨ller cells. Mu ¨ller cells subsequently transform glutamate into glutamine by the enzyme glutamine synthetase (GS). Ischemia of the retina leads to changes in the localization of the retinal amino acid neurotransmitters glutamate and GABA as well as to accumu- lation of glutamate and GABA in Mu ¨ller cells (Napper et al., 2001; Napper and Kalloniatis, 1999). Glutamate toxicity is considered to be caused by an excessive activation of the NMDA glutamate receptor, leading to an increased calcium influx, finally resulting in cell death (Lipton, 2004). In cat eyes with experimental retinal detachment, a marked decrease in the expression of glutamine synthetase (GS) * This study was supported by the Algemene Nederlandse Vereniging ter Voorkoming van Blindheid. The authors have no proprietary interest related to this article. * Corresponding author. Eye Research Institute Maastricht, Department of Ophthalmology, University Hospital Maastricht, P.O. Box 5800, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. Tel.: þ31 43 3875646; fax: þ31 43 3875343. E-mail address: r.diederen@np.unimaas.nl (R.M.H. Diederen). 0014-4835/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.exer.2005.10.031 Experimental Eye Research 83 (2006) 45e50 www.elsevier.com/locate/yexer