GDF-5调控视网膜干细胞迁移和分化的分子机制研究

At present, the challenge of retinal stem cell transplantation for the treatment of glaucoma is how to effectively promote the transplanted retinal stem cells to migrate, to differentiate into mature retinal ganglion cells, and to integrate into the local neuronal networks. During the initial in vitro and in vivo screening for the important factors that might regulate the retinal stem cell migration and differentiation, we identified growth differentiation factor (GDF-5) as a potential pro- migration and –differentiation factor despite its molecular mechanisms still awaits further study. We aim to screen for GDF-5 downstream genes or signaling pathways that regulate the migration and differentiation process based on Gene chip and Phospho-kinase antibody array analysis, to validate the biological function of these candidate genes and signaling pathways, and to substantiate the molecular mechanisms of GDF-5 function. Finally, in order to demonstrate the protection and improvement of visual function on retinal ganglion cells, we will intravitreally transplant the HyA xerogels loaded with GDF-5 and retinal stem cells in a rat glaucoma model, which may provide a strong theoretical basis for clinical stem cell therapy for glaucoma.

视网膜干细胞移植治疗青光眼的难点是能否有效促进移植的视网膜干细胞迁移分化为成熟的视网膜神经节细胞，并与靶组织特定神经元建立功能联系。我们前期工作利用已有的体内/体外模型筛选发现生长分化因子（GDF-5）可促进视网膜干细胞迁移，是一个潜在的调控视网膜干细胞迁移和分化的因子，然而其分子机制尚需进一步研究。本研究拟利用基因芯片技术和磷酸化激酶抗体阵列膜技术筛选GDF-5下游调控视网膜干细胞迁移和分化的关键靶基因和信号通路，验证关键靶基因和信号通路的功能，并初步阐明GDF-5发挥功能的分子机制。最后我们将载入GDF-5和HyA凝胶的视网膜干细胞移植到青光眼模型鼠玻璃体腔内，探讨此种移植对视网膜神经节细胞保护作用及视功能的改善情况，为临床青光眼的干细胞治疗提供强有力的理论依据。