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Y Kitaoka, T Kumai, K Isenoumi, S Kobayashi, S Ueno; Diverse Expressions of C-fos and Tyrosine Hydroxylase Following NMDA-induced Neurotoxicity in the Rat Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1450.
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Purpose:Activation of NMDA receptor is known to cause neuronal cell degeneration. We noted the relation between dopaminergic systems and NMDA-induced neurotoxicity. Tyrosine hydroxylase (TH) is a rate-limiting enzyme of dopamine synthesis. The aim of present study is to investigate whether TH related to the NMDA-induced neurotoxicity in the rat retina. The expression of TH was compared with the expression of c-fos that is inducted in response to the excitotoxin.Methods:Anesthetized rats (10 weeks of age) were given 200nM of NMDA in PBS intravitreally. Control eyes were injected with PBS. The eyes were enucleated after 1, 3 and 5 days of injection. Total RNA of retina was extracted by guanidium-cecium chloride methods. The expressions of TH mRNA and Thy-1 mRNA were assessed as compared with GAPDH using semi-quantitative RT-PCR. Moreover the expressions of TH protein and c-fos protein were examined by Western blot analysis. Results:NMDA treatment caused significant decreases in the expression of TH mRNA at 1,3 and 5 days after NMDA injection in rat retina. Similar results were obtained with the Thy-1 mRNA. Western blot analysis also showed a decrease in the expression of TH protein by exposing to NMDA. However, the expression of c-fos protein increased to a peak at 1 day after NMDA injection, then decreased to the control level at 3 and 5 days after injection. Conclusion:These findings indicate the vulnerability of dopaminergic system to excitatory amino acid in the rat retina. Transient induction of c-fos and sequential decrease in TH may be crucial events for NMDA-induced neurotoxicity in retina.
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