Wan Jin, Zheng Hua, Chen Zu-Lin, Xiao Hong-Lei, Shen Zhen-Jue, Zhou Guo-Min
Department of Anatomy, Histology and Embryology, Shanghai Medical School, Fudan University, 200032 Shanghai, China.
Vision Res. 2008 Jan;48(2):223-34. doi: 10.1016/j.visres.2007.11.002. Epub 2007 Dec 21.
To determine whether photoreceptor degeneration can stimulate Müller glia to transdifferentiate into neurons in adult mammalian retina, N-methyl-N-nitrosourea (MNU) was injected to induce complete loss of photoreceptors. Following MNU administration, Müller glia underwent reactive gliosis characterized by up-regulation of glial fibrillar acidic protein and nestin, and initiated proliferation through the cyclin D1 and D3 related pathways. Some Müller glia-derived cells were induced to express rhodopsin exclusively. These rhodopsin-positive cells exhibited synaptophysin around them, suggesting possible formation of synapses. After transplanted in to damaged retina, Müller glia migrated, grafted in host retina and produced rhodopsin. These results suggest that degeneration may promote preferential differentiation of Müller glia to photoreceptors and provide a potential therapeutic strategy for retinal degenerative diseases.
为了确定光感受器变性是否能刺激成年哺乳动物视网膜中的穆勒胶质细胞转分化为神经元，注射N-甲基-N-亚硝基脲（MNU）以诱导光感受器完全丧失。给予MNU后，穆勒胶质细胞发生反应性胶质增生，其特征是胶质纤维酸性蛋白和巢蛋白上调，并通过细胞周期蛋白D1和D3相关途径开始增殖。一些源自穆勒胶质细胞的细胞被诱导仅表达视紫红质。这些视紫红质阳性细胞周围出现突触素，表明可能形成了突触。移植到受损视网膜后，穆勒胶质细胞迁移、植入宿主视网膜并产生视紫红质。这些结果表明，变性可能促进穆勒胶质细胞向光感受器的优先分化，并为视网膜退行性疾病提供一种潜在的治疗策略。
