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K. Kuribayashi, T. Kumai, Y. Kitaoka, Y. Munemasa, J. Kogo, Y. Kitaoka, M. Motoki, S. Kobayashi, S. Ueno; The Improving Mechanism of Atrial Natriuretic Polypeptide on NMDA–Induced Neurotoxicity of Rat Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3094.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously reported that atrial natriuretic polypeptide (ANP) increased tyrosine hydroxylase (TH) protein, a rate limiting enzyme of catecholamine synthetic pathway, which improved NMDA–induced retinal neurotoxicity. However, the mechanisms of the increases of TH protein by ANP are unclear. We localized ANP receptors in rat retina and investigated whether ANP affects mRNA of TH. Methods: Male Wistar rats (8–weeks–old) were used in this study. A single 5 micro litter injection of 4×10–2 M NMDA with or without / 0.021 mM or 0.21 mM of ANP was administered intravitreally into one eye of anesthetized rat. Phosphate–buffered saline (PBS) was used as a control. The eyes were enucleated at 1 or 5 days after injection. Immunohistochemistry was performed with an antibody against ANP receptor using the DAB detection method. TH mRNA and TH protein levels were analyzed by quantitative real time–PCR and Western blot analysis, respectively. Results: ANP receptor was localized in ganglion cell layer (GCL), inner nuclear layer (INL) and outer nuclear layer (ONL) in rat retina. TH protein level and TH mRNA level in NMDA–treated retina were significantly lower than those of control retina. On the other hand, ANP significantly recovered NMDA–induced reduction of TH protein and TH mRNA levels.Conclusions: We confirmed that NMDA–induced reduction of TH protein and mRNA levels were recovered by ANP in rat retina. We also found that the ANP receptor was localized in GCL, INL and ONL by immunohistochemistry. These results suggest that ANP may exert neuroprotective effect through their receptors and the activation of TH gene transcription in NMDA–induced retinal neurotoxicity.
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