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J.-S. Choi, K.-A. Kim, Y. Cho, S.-J. Kim, C.-K. Joo; Morphological Damage of Photoreceptor Outer Segments in Rat Retina by Theophylline. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1347.
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In order to reveal photoreceptor toxicity as a result of theophylline intoxication, we studied the role of retinal guanylyl cyclase (Ret-GC) and soluble GC (sGC). Theophylline is a non-specific inhibitor of phosphodiesterase (PDE).
Sprague dawley rats were used for theophylline toxicity. The drug was administrated by intraperitoneal injection and the toxic effects were observed at 24 hrs after drug administration. To observe photoreceptor injury, light and electron microscopy were both used. And alteration of gene expression was confirmed by western blot analysis and RT-PCR.
Theophylline induced the degeneration of photoreceptor outer segments 24hrs after drug administration. The toxic effect of theophylline showed dose dependently. And theophylline altered gene expression in photoreceptor. Such as, rhodopsin kinase and recoverin expression are decreased and arrestin and guanylyl cyclase were increased by theophylline. Furthermore, cGMP dependent kinase(cGK) expression level was observed for cGMP mediated cell death by GC activation. The cGK protein and cGMP was increased in this study.
In this study, theophylline induced morphological change of photoreceptors segments. We also found that theophylline stimulates GC expression and cGMP formation in the retina. Therefore, these results suggest that GC plays a major role in theophylline induced photoreceptor degeneration.
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