携带人来源melanopsin光基因化视网膜前体细胞构建及其挽救视网膜色素变性大鼠视功能的研究

视网膜变性疾病是一类严重的致盲性眼病。干细胞移植的细胞替代疗法对于视网膜变性具有良好的临床应用前景，但功能改善以早期为主。干细胞在体移植后转归为感光细胞及内层神经元，变性晚期转归感光细胞光敏感性降低，且转归视网膜内层神经元数量有限，晚期视功能改善仍是难题。光基因技术的兴起为解决这一问题提供了可能。光基因转染可增加细胞光敏性，且绿藻来源的chr2光基因可促神经干细胞向神经元分化，人来源melanopsin光基因是否同样可促前体细胞向神经元转归是解决晚期功能改善的前题。且视网膜前体细胞在体移植后功能改善的突触机制也未见报道。本课题旨在构建人来源melanopsin光基因化视网膜前体细胞，研究其对干细胞的促神经元转归作用，并探讨其对色素变性大鼠晚期视功能的改善及突触重塑机制与离子通道机制。

The death of photoreceptor cells caused by retinal degenerative diseases often results a complete loss of retinal responses to light.Stem cell based therapies are a potential avenue for treatment of retinaldisease.Understanding the detailed mechanisms that govern stem cells fate between self-renewal and differentiation has been an urgent task for both basic research and clinicalapplications. But in recent years, a kind of special retinal ganglion cells were found, they express the melanopsin and are intrinsically photosensitive, so called intrinsically photosensitive ganglion cells (ipRGC). At first, melanopsin was considered to be involved in circadian rhythm modulation of sleep and alertness, and within few years it evident that these photoreceptors mediate irradiance detection for behavioral and physiological responses to light.Stem cell-based optogeneticstechnology represents a significant advancement in regulating the physiological state of stem cells. Thus, we want to examine whether the change in ion flux induced by light could trigger the transition of melanopin-Retinal Progenitor Cells fate from self-renewal to differentiation and inhibit theproliferation and cell cycle progress.Even,whether the melanopin-Retinal Progenitor Cells can restore the visual function is unknown.So,we want to do the research on whether the human-melanopsin Retinal Progenitor Cells can restored the visual function of retinal degeneration models and discuss the chang of the Ca+ ion flux and the mechanism of synaptic remodeling.