Study of molecular pathology of rat model with inherited retinal degeneration

皇家外科学院(Royal College of Surgeons，RCS)大鼠是目前研究最广泛的遗传性视网膜变性的分子病理动物模型，如视网膜色素变性(retinis dymentosa，RP)。本研究旨在评价几种钙拮抗剂对RCS大鼠视网膜退行性变的治疗作用。方法：采用地尔硫卓、尼卡地平、尼伐地平和硝苯地平等几种钙拮抗剂对大鼠视网膜进行治疗，观察视网膜的形态和功能。结果：在RCS大鼠视网膜变性初期，单纯尼伐地平全身给药可使视网膜形态和视网膜电信号恢复正常。免疫组织化学、逆转录聚合酶链式反应和Western blotting研究显示，尼伐地平治疗组大鼠视网膜视紫红质激酶和α-A蛋白表达显著增强。根据这些数据，尼伐地平有利于RCS大鼠光感受器细胞的保存，并有可能用于某些RP患者的治疗。

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.