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H. Yamazaki, H. Ohguro, I. Ohguro, K. Mamiya, F. Ishikawa, T. Metoki, Y. Miyagawa, Y. Takano, T. Ito, M. Nakazawa; Study of drug effects of dihydropyridine Ca2+ antagonists on retinal degeneration in Royal College Surgeons rat . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3584.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:The Royal College of Surgeons (RCS) rat is the most extensively studied animal model for understanding the molecular pathology of inherited retinal degeneration, such as retinitis pigmentosa (RP). In our recent study, we have found that some types of Ca2+ antagonists may potentially have preservation effects on RCS retinal degeneration. Here, in order to further study drug effects of several types dihydropyridine (DHP) (L–type, N–type, P/Q–type and R–type) of Ca2+ antagonist, which are most frequently used for treatment of hypertension in our clinic, on the retinal degeneration of RCS rats. Methods: Several types of DHP Ca2+ antagonists, nicardipine, nilvadipine, nifedipine, cilnidipine, and amlodipine were intraperitoneal administrated and thereafter retinal morphology and functions were analyzed. Results: We found that systemic administration of only nilvadipine among these Ca2+ antagonists caused preservation of retinal morphology and functions of electroretinogram responses in RCS rats during the initial stage of the retinal degeneration. Studies using immunohistochemistry, RT–PCR and Western blotting revealed significant enhancement of rhodopsin kinase and a–A–crystalline expressions, and suppression of caspase 1 and 2 expressions in the retina of nilvadipine treated rats. Conclusions: Based upon these data, it is suggested that nilvadipine is beneficial for the preservation of photoreceptor cells in RCS rats and can potentially be used to treat some RP patients.
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