视网膜Müller细胞的内源性神经干细胞特性研究进展

The advance of endogenous neural stem cell features for retinal Müller cell

神经干细胞(N S C)是一类能向神经细胞和胶质细胞分化的特殊干细胞。Miiller细胞作为视网膜主要内源性N S C ,具有在视网膜损伤后进入细胞周期增生并分化为神经细胞的能力。在脊椎动物中,视网膜 Miiller细胞的内源性NSC自发再生有着很高的效率,而哺乳动物这一能力几乎完全消失。深入研究发现,A scii、Sox2、Lin28、Atoh7等部分转录因子具有促进Miiller细胞增生并分化为神经细胞的功能。而Ascii联合组蛋白脱乙酰酶抑制剂更能使小鼠Mtiller细胞分化的神经细胞整合进入已有的视网膜并能对光做出反应,从而可能挽救视力。但与斑马鱼相比,哺乳动物 Mailer细胞增生再生能力依然十分有限。寻找更多能增强Miiller细胞分化能力的新因子将成为亟待解决的重要问题。

Neural stem cell is a kind of stem cells that can differentiate into neural and glial cells. While Müller cells, the main endogenous neural stem cell in retina,have the features to reentry into the cell cycle and differentiate into neural cells after retinal damage. Although it is highly effective for retinal Müller cell differentiation spontaneously after retinal injury in vertebrates, this feature is rigorous restricted in mammals. Recently, some transcription factors,such as Ascl1, Sox2, Lin28, Atoh7, are sufficient to drive quiescent Müller cells back in proliferation to generate new retinal neurons. Moreover, combining Ascl1 expression with a histone deacetylase inhibitor can bypass the limitation and increase the generation of new neurons in the adult retina. These regenerated neurons integrate the existing neuronal network and are able to respond to light, indicating that they can likely be used to restore vision. While these results are extremely promising, the regenerative response is still limited, likely because the proliferative capacity of mammalian Müller cells is low compared to their zebrafish counterparts. It is indeed necessary to identify new factors increasing the efficiency of the regenerative response.