Neurog2诱导重编程的Müller细胞治疗视网膜变性疾病的研究

替代变性凋亡的光感受器细胞是针对视网膜变性疾病的根本治疗之策。目前采用移植胚胎干细胞或者诱导性多功能干细胞治疗视网膜变性疾病的动物研究已有报道，但若将之在临床上推广应用在安全性和有效性方面仍有待提高。本项目将首次采用外源性导入basic helix-loop-helix (bHLH) 家族转录因子Neurog2重编程小鼠Müller细胞为视网膜神经细胞（尤其是光感受器细胞），从功能学上探求其在治疗视网膜变性疾病上的应用前景；并进一步阐明重编程过程中Neurog2通过调控表观遗传修饰改写Müller细胞基因表达谱的分子生物学机制，旨在寻求Müller细胞重编程为视网膜神经细胞过程中关键的“Check”点，为视网膜变性疾病的细胞替代治疗提供新的的理论依据和方法。

Photoreceptor loss leads to irreversible blindness in retinal degenerative diseases, and cell replacement therapy is a potential strategy to promote vision restoration in patients suffering from these diseases. Although a few studies have reported improved vision in mice with retinal degeneration after transplantation of embryonic stem cells or induced-pluripotent stem cells, the safety and efficiency of using cell transplantation to treat retinal degenerative diseases need to be improved before clinical trails in humans. In this project, we try to reprogram mouse Müller cells into functional retinal neurons (especially photoreceptor cells) using basic helix-loop-helix (bHLH) transcription factor Neurog2. We also further determine whether transplantation of Neurog2-reprogrammed Müller cells can actually restore some functional vision in mice subjected to sodium iodate (SI)-induced retinal degeneration. We finally take our analysis to a deeper level, examining how Neurog2 reprograms Müller cells through regulating epigenetic modifications of downstream target genes. In sum, we aim to uncover the “check” points underlying the processes of Müller cells reprogramming, which highlights the importance of our studies.