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B. Arango-Gonzalez, J. Kaur, G. Eske, F. Paquet-Durand, E. Zrenner; Cyclic GMP, PDE6β and CREB Regulation in P23H-1 and S334ter-3 Mutant Rhodopsin Transgenic Rats in the Course of Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4060.
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Our focus lies on using two rhodopsin mutant rats as models for RP to delineate the sequence of events that lead to retinal degeneration. In the present study we examined the synthesis of Cyclic GMP (cGMP), and expression of phosphodiesterase 6 ß (PDE6ß) and cAMP response element binding protein (CREB) in P23H-1 and S334ter-3 Mutant Rhodopsin Transgenic Rats.
Retinas of P23H-1, S334ter-3 and CD rats were collected at different developmental ages (PN0 - PN30). Retinas were examined by immunohistochemistry on cryo- and paraffin- sections using specific antibodies against cGMP, PDE6ß, CREB and phosphoCREB.
Using a well validated antibody directed against cGMP (Tanaka et al. 1997), in both transgenic retinas, particularly in the S334ter-3 mutants, we observed an increased cGMP immunoreactivity in photoreceptor cell bodies, processes and segments compared to their age matched controls. Early in the postnatal development (PN12), immunostaining showed only a weak labelling in the ONL of wild type retinas. This staining disappeared after PN20. PDE6ß immunostaining was limited to the OS of photoreceptors in CD as well as in mutant rats. However, OS length in S334ter-3, was reduced as the degeneration progressed. CREB expression was found in the cells localized in the INL and GCL of CD retinas on all analysed ages. On the other hand, in P23H-1 or S334ter-3 retinas, the absence of CREB staining was clear. PhosphoCREB expression was observed on all cell layers in the retina in wild type animals, being more intense in the inner retina. In both mutant models, a decrease in the staining intensity in the inner retina and in the number of stained cells in the ONL was found.
Our results suggest a seemingly critical role of cGMP and CREB in photoreceptor degeneration mechanisms in rhodopsin transgenic rats. Further experiments are required to establish the cause of cGMP up-regulation and its contribution to photoreceptor degeneration.
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