PURPOSE: The Royal College of Surgeons (RCS) rat is the most extensively studied animal model for understanding the molecular pathology in inherited retinal degeneration, such as retinitis pigmentosa (RP). The purpose of the present study was to evaluate the pharmacologic effects of several Ca(2+) antagonists on the retinal degeneration of RCS rats. METHODS: Several Ca(2+) antagonists, diltiazem, nicardipine, nilvadipine, and nifedipine, were intraperitoneally administered and retinal morphology and functions analyzed. RESULTS: Among the Ca(2+) antagonists, only intraperitoneally administered nilvadipine preserved retinal morphology and electroretinogram responses in RCS rats during the initial stage of retinal degeneration. Studies using immunohistochemistry, RT-PCR, and Western blot analysis revealed significant enhancement of rhodopsin kinase and alphaA-crystallin expression and suppression of caspase 1 and 2 expression in the retina of nilvadipine-treated rats. CONCLUSIONS: These data suggest that nilvadipine is beneficial for the preservation of photoreceptor cells in RCS rats and can be used to treat some patients with RP.
PURPOSE: The Royal College of Surgeons (RCS) rat is the most extensively studied animal model for understanding the molecular pathology in inherited retinal degeneration, such as retinitis pigmentosa (RP). The purpose of the present study was to evaluate the pharmacologic effects of several Ca(2+) antagonists on the retinal degeneration of RCS rats. METHODS: Several Ca(2+) antagonists, diltiazem, nicardipine, nilvadipine, and nifedipine, were intraperitoneally administered and retinal morphology and functions analyzed. RESULTS: Among the Ca(2+) antagonists, only intraperitoneally administered nilvadipine preserved retinal morphology and electroretinogram responses in RCS rats during the initial stage of retinal degeneration. Studies using immunohistochemistry, RT-PCR, and Western blot analysis revealed significant enhancement of rhodopsin kinase and alphaA-crystallin expression and suppression of caspase 1 and 2 expression in the retina of nilvadipine-treated rats. CONCLUSIONS: These data suggest that nilvadipine is beneficial for the preservation of photoreceptor cells in RCS rats and can be used to treat some patients with RP.
Authors: Vincent T Ciavatta; Moon Kim; Paul Wong; John M Nickerson; R Keith Shuler; George Y McLean; Machelle T Pardue Journal: Invest Ophthalmol Vis Sci Date: 2009-03-05 Impact factor: 4.799