Abstract
Purpose
Vitreous and retinal amino-acid concentrations were evaluated in a primate model of central retinal artery occlusion (CRAO) to study the role of glutamate excitotoxicity in acute retinal ischaemia.
Methods
Unilateral, acute CRAO was produced by temporary clamping of the central retinal artery for 190?min in four elderly rhesus monkeys. Fundus photography, fluorescein angiography, and electroretinogram were performed before and during CRAO, and after unclamping the artery. Vitreous samples were obtained before and after CRAO in both eyes, and analysed for 13 amino-acid concentrations using high-pressure liquid chromatography. The animals were killed 350?min after retinal reperfusion, and the retinal tissue was submitted for amino-acid analysis.
Results
In all four eyes, the macula showed the ‘cherry red spot’. The CRAO was confirmed by fluorescein angiography and decreased b-wave on electroretinogram. Retinal histology confirmed ischaemic changes in the inner retina. Changes in all 13 vitreous amino-acid concentrations after CRAO (including glutamate) were not significantly different between study and control eyes (P=0.09 to 0.82). All retinal amino-acid concentrations (including glutamate) were not significantly different between two eyes (P=0.07–0.93).
Conclusions
In the primate model of acute inner retinal ischaemia induced by transient CRAO, we were unable to detect significantly elevated concentrations of vitreous and retinal glutamate. Our primate model has the advantage of closely modelling the CRAO in humans. Further basic and clinical studies are needed to elucidate the role of glutamate excitotoxicity in retinal ischaemia.
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References
Hayreh SS, Jonas JB . Optic disk and retinal nerve fiber layer damage after transient central retinal artery occlusion: an experimental study in Rhesus monkeys. Am J Ophthalmol 2000; 129: 786–795.
Hayreh SS, Kolder HE, Weingeist TA . Central retinal artery occlusion and retinal tolerance time. Ophthalmology 1980; 87: 75–78.
Ffytche TJ . A rationalization of treatment of central retinal artery occlusion. Trans Ophthalmol Soc UK 1974; 94: 468–479.
Duker JS, Brown GC . Recovery following acute obstruction of the retinal and choroidal circulations. A case history. Retina 1988; 8: 257–260.
Mangat HS . Retinal artery occlusion. Surv Ophthalmol 1995; 40: 145–156.
Pycock CJ . Retinal neurotransmission. Surv Ophthalmol 1985; 29: 355–365.
Choi DW . Glutamate neurotoxicity and diseases of the nervous system. Neuron 1988; 1: 623–634.
Bresnick GH . Excitotoxins: a possible new mechanism for the pathogenesis of ischemic retinal damage. Arch Ophthalmol 1989; 107: 339–341.
Mosinger JL, Price MT, Bai HY, Xiao H, Wozniak DF, Olney JW . Blockade of both NMDA and non-NMDA receptors is required for optimal protection against ischemic neuronal degeneration in the in vivo adult mammalian retina. Exp Neurol 1991; 113: 10–17.
Gupta LY, Marmor MF . Mannitol, dextromethorphan, and catalase minimize ischemic damage to retinal pigment epithelium and retina. Arch Ophthalmol 1993; 111: 384–388.
Hayreh SS, Weingeist TA . Experimental occlusion of the central artery of the retina. I. Ophthalmoscopic and fluorescein fundus angiographic studies. Br J Ophthalmol 1980; 64: 896–912.
Russell SR, Hageman GS . Optic disc, foveal, and extrafoveal damage due to surgical separation of the vitreous. Arch Ophthalmol 2001; 119: 1653–1658.
Miller MW, Waziri R, Baruah S, Gilliam DM . Long-term consequences of prenatal cocaine exposure on biogenic amines in the brains of mice: the role of sex. Brain Res Dev Brain Res 1995; 87: 22–28.
Lagreze WA, Knorle R, Bach M, Feuerstein TJ . Memantine is neuroprotective in a rat model of pressure-induced retinal ischemia. Invest Ophthalmol Vis Sci 1998; 39: 1063–1066.
Adachi K, Kashii S, Masai H, Ueda M, Morizane C, Kaneda K et al. Mechanism of the pathogenesis of glutamate neurotoxicity in retinal ischemia. Graefes Arch Clin Exp Ophthalmol 1998; 236: 766–774.
Louzada-Junior P, Dias JJ, Santos WF, Lachat JJ, Bradford HF, Coutinho-Netto J . Glutamate release in experimental ischaemia of the retina: an approach using microdialysis. J Neurochem 1992; 59: 358–363.
Muller A, Villain M, Bonne C . The release of amino acids from ischemic retina. Exp Eye Res 1997; 64: 291–293.
Napper GA, Pianta MJ, Kalloniatis M . Reduced glutamate uptake by retinal glial cells under ischemic/hypoxic conditions. Vis Neurosci 1999; 16: 149–158.
Kawasaki A, Otori Y, Barnstable CJ . Muller cell protection of rat retinal ganglion cells from glutamate and nitric oxide neurotoxicity. Invest Ophthalmol Vis Sci 2000; 41: 3444–3450.
Levkovitch-Verbin H, Quigley HA, Kerrigan-Baumrind LA, D’Anna SA, Kerrigan D, Pease ME . Optic nerve transection in monkeys may result in secondary degeneration of retinal ganglion cells. Invest Ophthalmol Vis Sci 2001; 42: 975–982.
Carter-Dawson L, Crawford ML, Harwerth RS, Smith III EL, Feldman R, Shen FF et al. Vitreal glutamate concentration in monkeys with experimental glaucoma. Invest Ophthalmol Vis Sci 2002; 43: 2633–2637.
Kalloniatis M . Amino acids in neurotransmission and disease. J Am Optom Assoc 1995; 66: 750–757.
Acknowledgements
We acknowledge the excellent technical support provided by Ms Donna McAllister and Trish Duffel. This work was supported in part by University of Iowa College of Medicine Research Award, the Shaffer International Research Fellowship from Glaucoma Research Foundation, and unrestricted grant from Research to Prevent Blindness, New York, New York. SSH is a Research to Prevent Blindness Senior Scientific Investigator.
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Presented in part at the Association for Research in Vision and Ophthalmology meeting, Fort Lauderdale, FL, April 2001
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Kwon, Y., Rickman, D., Baruah, S. et al. Vitreous and retinal amino acid concentrations in experimental central retinal artery occlusion in the primate. Eye 19, 455–463 (2005). https://doi.org/10.1038/sj.eye.6701546
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DOI: https://doi.org/10.1038/sj.eye.6701546
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