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Y Izumi, M Ishikawa, AM Benz, M Izumi, CF Zorumski; The Mechamism of Müller Cell . Invest. Ophthalmol. Vis. Sci. 2002;43(13):670.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: It is widely accepted that glutamate (Glu)-mediated excitotoxic neuronal degeneration is involved in various retinal disorders. However, under normal conditions the retina can be exposed to high concentrations of exogenous Glu without toxic consequences. In a rat retinal preparation, Glu, at concentrations up to 1 mM, induces Müller cell swelling but not excitotoxic neuronal damage. The reversibility of Müller cell swelling after Glu washout indicates that Müller cell swelling is not a toxic consequence. It is presently unclear whether Glu directly induces Müller cell swelling. It is possible that glutamine (Gln), a metabolite of Glu, induces Müller cell swelling by acting as an osmolyte. To examine this possibility, we used methionine sulfoximine (MSO), an inhibitor of glutamine synthetase, the enzyme that catalyzes the synthesis of Gln from Glu and ammonia. Methods: Ex vivo rat retinas were exposed to 1mM Glu or 1mM Gln. Glu was combined with 1 mM ammonia or with MSO. Results were analyzed histologically. Results:Glu-mediated Müller cell swelling was masked by co-administration of ammonia. The reversibility of Müller cell swelling was blocked by MSO following 20 min administration of Glu. Gln alone failed to induce Müller cell swelling. Conclusion: Glu-mediated Müller cell swelling is unlikely to result from accumulation of Gln. Rather, metabolism to Gln is crucial for reversibility of Glu-mediated Müller cell swelling. Although ammonia can be toxic to the CNS, ammonia is necessary for Glu metabolism. These observations suggest that the metabolism of Glu to Gln is important for controlling Glu-mediated toxicity in the retina.
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