Study of molecular pathology of rat model with inherited retinal degeneration

皇家外科医学院（RCS）大鼠是用于理解遗传性视网膜变性（例如视网膜色素变性（RP））的分子病理学的最广泛研究的动物模型。本研究旨在观察几种钙拮抗剂对RCS大鼠视网膜变性的影响。方法：<2a>腹腔注射地尔硫卓、尼卡地平、尼伐地平、硝苯地平等钙拮抗剂，观察视网膜形态和功能。结果如下：我们发现，在RCS大鼠视网膜变性的初始阶段，仅全身给予尼伐地平可使视网膜的形态和视网膜电图反应的功能得到保护。免疫组化、RT-PCR和Western blotting结果显示，尼伐地平处理组大鼠视网膜视紫红质激酶和α-A-晶体的表达明显增强。基于这些数据，强烈建议尼伐地平有利于RCS大鼠感光细胞的保存，并可能用于治疗某些RP患者。

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). Here, purpose of the present study is to evaluate drug effects of several kinds of Ca^<2+> antagonist on the retinal degeneration of RCS rats. Methods : Several kinds of Ca^<2a> antagonists, diltiazem, nicardipine, nilvadipine or niphedipine, were intraperitoneal administrated and thereafter retinal morphology and functions were analyzed. Results : We found that systemic administration of only nilvadipine caused preservation of retinal morphology and functions of electroretinogram resopnses 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 α-A-crystalline expressions in the retina of nilvadipine treated rats. Based upon these data, it is strongly suggested that nilvadipine is beneficial for the preservation of photoreceptor cells in RCS rats and can potentially be used to treat some RP patients.