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J.–S. Choi, C.–K. Joo; Guanylyl Cyclase Related Photoreceptor Degeneration in Theophylline Intoxication . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1686.
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Purpose: In order to prevent photoreceptor degeneration in theophylline intoxication, we investigated this study. Theophylline is a non–specific inhibitor of phosphodiesterase (PDE). Methods: Sprague dawley rats were used for theophylline toxicity. The drug applied by intraperitoneal injection, from low to sublethal dose. The toxic effects were observed from 24 hrs to 2 weeks after drug administration. To observe of photoreceptor degeneration, light and electron microscopy were used. Also, alteration of gene expression confirmed by western blot analysis and RT–PCR. Results: Theophylline induced photoreceptor cell death from 24hrs after drug administration. The effect of theophylline showed dose dependently. Up or down regulation on some gene were observed in theophylline intoxication. Such as, rhodopsin kinase and recoverin expression are decreased and arrestin and ret–GC were increased by theophylline. Furthermore, cGMP dependent kinase(cGK) expression level was observed for cGMP mediated cell death by ret–GC activation. The cGK protein level was increased in this study.Conclusions:Theophylline inhibits phosphodiesterase. And then, cGMP level is increased in cells. In this study, we found that theophylline induce ret–GC expression and cGMP formation in the retina. Therefore, we suggest that ret–GC play a major role in theophylline induced photoreceptor degeneration.
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