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J.-S. Choi, C.-K. Joo; Activation of Calpain D and Caspase in the Elevated cGMP Mediated Photoreceptor Injury. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4402. doi: https://doi.org/.
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In order to reveal therapeutic mechanism in photoreceptor injury as a result of elevated cGMP, 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 induced photoreceptor toxicity. The drug was administrated by intraperitoneal injection. 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 cGMP level was increased after theophylline administration. Expression of calpain D and caspase were increased in elevated cGMP mediated photoreceptor injury. Furthermore, cGMP dependent kinase(cGK) expression level was increased for photoreceptor injury. Suppression of guanylyl cyclase inhibited activation of caspase and photoreceptor damage.
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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