Study of molecular pathology of rat model with inherited retinal degeneration

遗传性视网膜变性大鼠模型的分子病理学研究

• 批准号: 13671846
• 负责人: OHGURO Hiroshi
• 金额: $ 2.43万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671846/
• 关键词: retinal degeneration; animal model; retinitis pigmentosa; drug therapy; calcium antagonist; photoreceptor; recoverin; rhodopsin phosphorylation; 癌関連網膜症; 自己免疫; ロドプシンキナーゼ; 光情報伝達; RCSラット; Ca拮抗財; アポトーシス; 網膜電位図; 神経保護

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.

为了了解遗传性视网膜变性（如色素性视网膜炎（RP））的分子病理学，英国皇家外科医学院（RCS）大鼠是研究最广泛的动物模型。本研究旨在评价几种Ca^<2+>拮抗剂对RCS大鼠视网膜变性的药物作用。方法：分别给药地尔硫卓、尼卡地平、尼伐地平和尼苯地平，观察大鼠视网膜形态和功能。结果：我们发现，在RCS大鼠视网膜变性初期，全身只给药尼伐地平可以保留视网膜形态和视网膜电图反应功能。免疫组织化学、RT-PCR和Western blotting研究显示，尼伐地平处理大鼠视网膜中rhodopsin kinase和α- a -crystal的表达显著增强。基于这些数据，我们强烈建议尼伐地平对RCS大鼠的光感受器细胞的保存有益，并可能用于治疗一些RP患者。

项目成果

Ohguro, H., Nakazawa, M.: "Pathological roles of recoverin in Cancer-associated retinopathy"Photoreceptor and calcium (LANDES Bioscience). 625 (2002)

Ohguro, H., Nakazawa, M.：“恢复蛋白在癌症相关视网膜病变中的病理作用”光感受器和钙（LANDES Bioscience）。

Maeda T., et al.: "Mechanisms of photoreceptor cell death in cancer-associated retinopathy"Invest Ophthalmol Vis Sci. 42. 709-712 (2001)

Maeda T. 等人：“癌症相关视网膜病变中感光细胞死亡的机制”Invest Ophasemol Vis Sci。

Ohguro, H., Maruyama, I., Nakazawa, M., Oohira, A.: "Presence of anti-recoverin antibody within aqueous humor in patient with cancer-associated retinopathy"Am J Ophthalmol. 134. 605-607 (2002)

Ohguro, H.、Maruyama, I.、Nakazawa, M.、Oohira, A.：“癌症相关视网膜病变患者房水中存在抗恢复蛋白抗体”Am J Ophamol。

Maruyama, I., Maeda, T., Okisaka, S., Mizukami, A., Nakazawa, M.Ouguro, H.: "Autoantibody against neuron-specific enolase found in glaucoma patients causes retinal dysfunction in vivo"Jpn J Ophthalmol. 46. 1-12 (2002)

Maruyama, I.、Maeda, T.、Okisaka, S.、Mizukami, A.、Nakazawa, M.Ouguro, H.：“在青光眼患者中发现的针对神经元特异性烯醇化酶的自身抗体会导致体内视网膜功能障碍”Jpn J Ophthalmol。

Ikeda Y, Maruyama I, Nakazawa M, Ohguro H: "Clinical significance of serum antibody against neuron-specific enolase in glaucoma patients."Jpn J Ophthalmol. 46. 13-17 (2002)

Ikeda Y、Maruyama I、Nakazawa M、Ohguro H：“青光眼患者神经元特异性烯醇化酶血清抗体的临床意义。”Jpn J Ophamol。