视网膜色素变性（RP）是一组遗传性进行性视网膜变性疾病，目前临床尚无有效的防治措施。新近研究发现，光遗传学技术是极具前景的治疗方法，但治疗后视功能的改善仅能通过视网膜电图、视觉诱发电位等方法整体粗略地评估。因此，迫切需要一种可以全面、具体、深入地评估治疗前、后RP患者球后视路各解剖部位结构、功能和生化代谢变化的新技术。我们前期研究发现，多模态功能磁共振（fMRI）可定量检测双眼盲大鼠视路轴索退变、神经元兴奋性下降和神经递质异常，因此，本项目拟采用多模态fMRI结合电生理、行为学及组织学方法，分别研究光遗传学（melanopsin基因）治疗前、后不同时间点RCS大鼠（RP经典模型）视路及相关脑区的结构与功能连接、全脑网络和代谢标志物等改变，以明确多模态fMRI在疗效评价中的作用，阐明其视功能恢复的动态变化规律及发生机制，并为多模态fMRI应用于RP等视网膜退行性疾病的临床诊治提供理论依据。

Retinitis pigmentosa (RP) is a group of hereditary progressive retinopathy. Currently, there is no effective methods in the prevention and treatment for RP in clinic. Recent studies have suggested that otogenetics is the most promising method for treating RP patients. However, the improvement of visual function after the treatment can only be integrally and roughly accessed by electroretinogram and visual evoked potential examinations. Therefore, it is very urgent to find a new technique, which can comprehensively, concretely and deeply evaluate the structural, functional and metabolic changes of each part in the visual pathway of RP patients before and after otogentics treatment. Our previous studies have shown that multi-modal functional MRI can quantitatively detect the axonal degeneration of nerve fibers in the visual pathway, the decrease of neuronal excitability and abnormal levels of neurotransmitters in the binocularly blind rats. Thus, this project aims to investigate the changes of structural, functional connections, whole brain network and metabolic biomarker in the visual pathway and related brain regions in RCS rats (the classic animal model of RP) at different stages of pre- and post-treatment with otogenetics (melanopsin gene) therapy by using multi-modal functional MR imaging combined with electrophysiological, behavioral experiments and histopathology to make clear the value of multi-modal functional MRI in the evaluation of the therapeutic effect. The goal of our project is also to explore the dynamic changes and mechanisms of visual functional recovery of RCS rats after treatment and to provide a theoretical basis for multi-modal functional MR imaging in the application of clinical diagnosis and treatment in the patients with RP and retinal degeneration diseases.