Nambu H, Yuge K, Nakajima M, Shikata N, Takahashi K, Miki H, Uyama M, Tsubura A
Department of Pathology, Kansai Medical University, Osaka, Japan.
Pathol Int. 1997 Jun;47(6):377-83. doi: 10.1111/j.1440-1827.1997.tb04511.x.
Morphologic characteristics of retinal degeneration induced by a single systemic administration of N-methyl-N-nitrosourea (MNU) in mice was investigated. The aim was to characterize the MNU-induced retinal lesions in mice and compare them with human retinitis pigmentosa. A dose of 60 mg/kg body weight MNU, injected intraperitoneally into male and female C57BL mice, evoked progressive retinal degeneration in all treated mice, while control mice remained normal. An early change was photoreceptor apoptosis followed by infiltration of macrophages and swelling of the pigment epithelial cells with phagosomal inclusions for apoptotic photoreceptor cell removal. Loss of the majority of photoreceptor cells occurred within a week. Then, Feulgen-positive corpuscles, indicative of an aggregation of degenerative photoreceptor elements, vitread the outer limiting membrane were surrounded by Müller cell processes, and the duplication of the pigment epithelial cells sclerad the outer limiting membrane were seen 2 and 3 weeks after the treatment. Finally, the Feulgen-positive corpuscles disappeared and Müller cell processes were in direct contact with the continuous lining of the single layer of pigment epithelial cells. As in retinitis pigmentosa in humans, the primary event was loss of photoreceptor cells by apoptosis, but the migration of the pigment epithelial cells within the retina was not seen in the present model.
研究了单次全身给予N-甲基-N-亚硝基脲（MNU）诱导的小鼠视网膜变性的形态学特征。目的是对MNU诱导的小鼠视网膜病变进行特征描述，并将其与人类色素性视网膜炎进行比较。将60mg/kg体重的MNU腹腔注射到雄性和雌性C57BL小鼠体内，所有处理的小鼠均出现进行性视网膜变性，而对照小鼠保持正常。早期变化是光感受器凋亡，随后是巨噬细胞浸润以及色素上皮细胞肿胀并伴有吞噬体包涵物以清除凋亡的光感受器细胞。大多数光感受器细胞在一周内丧失。然后，在治疗后2周和3周时，可见福尔根阳性小体（表明退行性光感受器元件聚集）向玻璃体方向穿过外限制膜并被Müller细胞突起包围，以及色素上皮细胞向巩膜方向增生穿过外限制膜。最后，福尔根阳性小体消失，Müller细胞突起与单层色素上皮细胞的连续内衬直接接触。与人类色素性视网膜炎一样，主要事件是光感受器细胞通过凋亡丧失，但在本模型中未观察到色素上皮细胞在视网膜内的迁移。
