视网膜光感受器凋亡后的光遗传学重建

视网膜色素变性，年龄相关性黄斑病变等眼底病可导致视网膜光感受器细胞的不可逆死亡。但光感受器死亡后，其下游还有大量的神经元残留，如双极细胞（BC）和神经节细胞（GC）等。如能利用剩下的神经细胞网络，则将重建视网膜的正常生理功能。我们拟通过AAV2病毒导入Cre酶依赖的光敏蛋白，在PCP2-Cre小鼠视网膜的ON-BC细胞上定向表达光敏蛋白通道。光敏蛋白可以控制ON-BC对光的反应，并将对光反应传输到下游的神经节细胞。前期工作中, 我们一方面鉴定了正常情况下ON-BC信号的传导机制，另一方面也分析了MNU诱导的视网膜光感受器凋亡后所剩下的视网膜网络。本项目旨在现有的工作基础上，利用光遗传学的方法建立新型的PCP2-ChR-2A-Halo：MNU动物模型，并通过诱导ON-BC上特异表达的光敏蛋白的反应来达到视网膜光感受器细胞凋亡后的视网膜网络重建。

Retinal disease like RP or AMD will lead to ultimate photoreceptor death. But there are still normal retinal neurons like bipolar cells or ganglion cells alive, with no signal input though. In this project, we propose to make the advantage of those residue neurons to reestablish retinal function. We would inject AAV2 virus that carry Cre-depended ChR2/Halo to PCP2-Cre mouse. So On-BC could be driven by light and then send the signal to the following neurons (ala. Ganglion cells). In our previous work, we have described ON-BC signal pathway in the healthy retina, we also described residue retinal pathway in the MNU induced photoreceptor degeneration. We will use optogenetics tool to establish PCP2-ChR-2A-Halo: MNU mice mouse model, to test the possible ability to reestablish ON-BC light response and retinal network when photoreceptors degenerated. We aim to pave the new way for photoreceptor retinal degeneration disease treatment.