由于哺乳动物视网膜缺少再生能力，多种视网膜疾病导致的视锥视杆细胞的不可逆退化严重影响患者视觉。因此寻找再生感光细胞的手段和方法就具有相当重要的意义。视锥视杆是一类特化的光感受细胞，要做到真正修复视觉的，在得到具有感光功能的细胞同时还需要保证它们能够和视网膜下游神经细胞形成偶联。申请人此前首次验证了感光细胞前体细胞移植得到的新生视杆的单细胞光反应。但是至今国际上尚没有有效再生视锥细胞的方法。鉴于此，本项目结合申请人在感光细胞电生理以及细胞再生方面的经验，将在小鼠模型上通过主动调节重要视锥视杆发育转录因子的方法，促使感光细胞前体细胞移植后的视锥再生。同时将深入研究前体细胞移植后再生的视锥视杆的细胞光反应和光信号转导特性，以及它们同视网膜下游神经细胞的功能性偶联情况。最终将使用此模型验证再生视锥对受损昼视觉的修复能力。本项目的研究将为今后的细胞替代治疗感光细胞退化提供理论依据和可能的途径。

The visual impairment caused by photoreceptor degeneration in many retinal diseases is still incurable because that the mammalian retinal photoreceptor cells lack the ability to regenerate. Therefore, it is important to find the ways to regeneration photoreceptors. Furthermore, in order to be fully functional in vivo, not only the photoreceptor cell itself need to be light sensitive, but also it should form the proper neuronal connections with downstream retinal neurons. Recently the applicant has demonstrated the light sensitivity from rod photoreceptors differentiated from transplanted retinal precursor cells. But So far, cone photoreceptors have not been convincingly produced by progenitor-cell transplantation. For human, however, cones are far more important for daily vision. Combining the applicant's expertise in photoreceptors electrophysiology and cellular regeneration, this project is intended to promote cone regeneration after progenitor cells transplantation by modulating the critical rods/cones differentiation transcription factor. In the same time, I will study in depth the light response, phototransduction and the functional integration of the newborn rod and cone photoreceptors with downstream retinal neurons. Finally, the ability of the newborn cones to rescue the impaired photopic vision will also be assessed. This study will eventually pave the way for future cell replacement therapy of the photoreceptor degeneration.