Comparative pathological study of human retinitis pigmentosa and its animal models

人视网膜色素变性及其动物模型的病理比较研究

• 批准号: 09671823
• 负责人: TSUBURA Airo
• 金额: $ 1.86万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671823/
• 关键词: Retinitis pigmentosa; nitrosomethylurea; apoptosis; photoreceptor cell; retinal degeneration; pigment epithelial cell; retinal dysplasia; rosette; ニトロソ尿素; アポトーシス; 視細胞; 実験動物; 色素上皮細胞

Retinal degeneration characterized by photoreceptor apoptosis was induced by a single systemic administration of N-methyl-N-nitrosourea (MNU) in a variety of adult animals : rodents (mouse, rat and hamster), insectivora (shrew ; Suncus murinus), and non-human primates (monkey ; Macaca Fuscata). Therefore, phylogenetically, MNU-induced photoreceptor apoptosis is a universal phenomenon. However, the lesions (similar to human retinitis pigmentosa) initiated from the equatorial zone in monkeys, whereas in the other species the lesions originated from the posterior pole. After the photoreceptor cell loss, an intraretinal migration of pigment epithelial cells was seen in rats and hamsters, but as in humans, the migrated pigment epithelial cells in contact with a blood vessel was seen only in the hamsters ; no pigment epithelial cell migration was seen in the mice, shrews or monkeys. Retinal dysplasia characterized by dysplastic rosettes was induced in mice treated with MNU at day 0 or 3 (the stage of retinal cell proliferation), whereas no retinal response was seen when MNU was administered at day 5 or 8 (the stage of retinal cell differentiation), and retinal degeneration occurred when MNU was administered at or over day 11 (after cellular differentiation). Thus, from the ontogenetic point of view, the MNU response was related to retinal development in that there was a critical period for the time of MNU administration for the induction of retinal lesions.

在多种成年动物中，通过单次全身给予N-甲基-N-亚硝基脲（MNU）诱导以感光细胞凋亡为特征的视网膜变性：啮齿动物（小鼠、大鼠和仓鼠）、食虫动物（鼩 鼱;臭鼩）和非人灵长类动物（猴;恒河猴）。因此，MNU诱导的光感受器细胞凋亡是一种普遍现象。然而，猴子的病变（类似于人类视网膜色素变性）起源于赤道区，而其他物种的病变起源于后极。感光细胞丧失后，在大鼠和仓鼠中观察到色素上皮细胞的视网膜内迁移，但与人类一样，仅在仓鼠中观察到与血管接触的迁移的色素上皮细胞;在小鼠、地鼠或猴中未观察到色素上皮细胞迁移。在第0天或第3天（视网膜细胞增殖阶段）用MNU处理的小鼠中诱导了以发育异常性视网膜病变为特征的视网膜发育不良，而当在第5天或第8天（视网膜细胞分化阶段）施用MNU时未观察到视网膜反应，并且当在第11天或超过第11天（细胞分化后）施用MNU时发生视网膜变性。因此，从个体发育的角度来看，MNU反应与视网膜发育有关，因为MNU给药诱导视网膜病变的时间有一个关键时期。

项目成果

Nambu H,Taomoto M,Ogura E and Tsubura A.: "Time-specific action of N-methyl-N-nitrosourea in the occurrence of retinal dysplasia and retinal cegeneration in neonatal mice." Pathol Int. 48(3). 199-205 (1998)

Nambu H、Taomoto M、Ogura E 和 Tsubura A.：“N-甲基-N-亚硝基脲在新生小鼠视网膜发育不良和视网膜再生中的时间特异性作用。”

Tsubura A,Yoshizawa K,Miki H,Oishi Y,Fujii T.: "Phylogenetic and ontogenetic study of retinal lesions induced by N-methyl-N-nitrosourea in animals." Anim Eye Res. 17(3/4). 97-103 (1998)

Tsubura A、Yoshizawa K、Miki H、Oishi Y、Fujii T.：“N-甲基-N-亚硝基脲诱导动物视网膜病变的系统发育和个体发育研究”。

Nambu H: "Time-specific action of N-methyl-N-nitrosourea in the occurrence of retinal dysplasia and retinal degeneration in neonatal mice." Pathol Int. 48(3). 199-205 (1998)

Nambu H：“N-甲基-N-亚硝基脲在新生小鼠视网膜发育不良和视网膜变性发生中的时间特异性作用。”

Taomoto M,Nambu H,Senzaki H,Shikata N,Oishi Y,Fujii T,Miki H,Uyama M and Tsubura A.: "Retinal degeneration induced by N-methyl-N-nitrosourea in Syrian golden hamsters." Graefe's Arch Clin Exp Ophthalmol. 236(9). 688-695 (1998)

Taimoto M、Nambu H、Senzaki H、Shikata N、Oishi Y、Fujii T、Miki H、Uyama M 和 Tsubura A.：“N-甲基-N-亚硝基脲诱导叙利亚金仓鼠视网膜变性。”

Nambu H: "Age-specific and dose-dependent retinal dysplasia and degeneration induced by a single intraperitoneal administration of N-methyl-N-nitrosourea." J Toxicol Pathol. 11(2). 127-131 (1998)

Nambu H：“单次腹膜内注射 N-甲基-N-亚硝基脲可引起年龄特异性和剂量依赖性视网膜发育不良和变性。”