视网膜Müller胶质细胞在体重编程治疗眼缺血综合征及机制研究

眼缺血综合征（ocular ischemic syndrome, OIS）由颈动脉供血不足所致的一系列颅内缺血和眼部缺血的临床综合征。OIS可造成永久性视力损伤，而现仍无有效治疗手段。基于在体谱系重编程技术的最新研究表明视网膜Müller细胞可在体内环境下重编程为多种视网膜神经元。我们在前期研究中发现OIS模型中视网膜各层细胞均减少。而Müller细胞经在体重编程后可否弥补OIS丢失的多种类型神经元，并修复宿主视功能？目前仍不清楚。本项目旨在研究在OIS的视网膜缺血环境中，利用逆转录病毒载体转染Ascl1配合曲古霉素-A诱导Müller细胞在体重编程，并检测Müller细胞重编程的效率，形成的神经元类型、功能和整合能力，以及对宿主视功能的修复作用及机制，进一步阐明Müller细胞在体重编程的机制。研究结果对理解Müller细胞激活的调控机制有重要意义，同时也为OIS的治疗提供新的理论依据。

Ocular ischemic syndrome (OIS) is a series of clinical syndromes of intracranial ischemia and ocular ischemia caused by inadequate carotid artery blood-supply insufficiency. OIS can cause permanent visual impairment, yet there is still no effective treatment. Recent studies based on in vivo reprogramming techniques show that Müller cells can be reprogrammed and differentiated into multiple retinal neurons in vivo. In the previous studies, we found all layers of retina in OIS model were reduced. Could reprogrammed Müller cells supplement varied types of dead neurons, and restore the visual function of the OIS host? It is still not clear. The purpose of this study was to apply retroviral vector of Ascl1 with trichostatin-A in the retina ischemia microenvironment, and then to investigate the efficiency of Müller cell reprogramming, the types, function and integration ability of neurons that reprogrammed Müller cell differentiate, , as well as the mechanism of host visual function, to further clarify the mechanism of Müller cells in vivo programming. The results of this study are not only of great significance on the regulation mechanism of Müller cell activation, but also provide a new theoretical basis for the treatment of OIS.