miRNA-23a调控年龄相关性黄斑变性发生的分子机制及杞灵颗粒的干预作用

Age-related macular degeneration （AMD）is the leading cause of severe vision loss in people over age 50. The pathogenesis of AMD remains unclear. Recent years studies show that epigenetics change caused by miRNA plays a critical role in the pathogenesis of AMD. MiRNA23a is closely related to oxidative stress response, which is the most important predisposing factor of AMD occurrence. Revealing the signal pathways and molecular mechanism of miRNA23a in regulating AMD pathogenesis will provide novel therapeutic targets for AMD treatment. Qi Ling Granules is an empirical formula commonly used in our clinics to treat AMD. Previous studies have proven that Qi Ling Granules could protect the retina from oxidative stress damage. It is very meaningful to figure out whether Qi Ling Granules plays antioxidant activity through reversing miRNA23a damage caused by oxidative stress. Therefore, we design this project to thoroughly investigate the molecular mechanism of miRNA-23a in regulating AMD pathogenesis as well as the intervention of Qi Ling Granules through Fas/FasL and Nrf2 /Keap1 /ARE pathway , using AMD mouse model induced by light and hydroquinone as study object, and research techniques such as cellular and molecular microbiology approaches and pathology, thus to provide reliable and scientific evidence for clinical application.

年龄相关性黄斑变性(AMD) 是50 岁以上人群视力丧失的主要病因，其发病机制尚未完全阐明。最近研究发现AMD发生与miRNA引起的表观遗传改变有关，其中miRNA-23a和氧化应激反应关系密切，后者是AMD发病的重要诱因，揭示miRNA调控AMD发生的分子机制将为AMD防治提供新靶点。杞灵颗粒是我们临床多年治疗AMD的经验方，前期研究发现可以保护视网膜氧化应激损伤。杞灵颗粒的抗氧化作用是否是通过逆转氧化应激因素导致的miRNA-23a异常改变而实现值得进一步探讨，本项目以可见光联合烟雾中主要成分氢醌为氧化应激因素诱导AMD动物模型，采用细胞分子生物学、病理学等现代研究技术，从Fas/FasL和Nrf2 /Keap1 /ARE两个信号通路深入探讨miRNA-23a调控AMD发生的分子机制及杞灵颗粒的干预作用，为临床防治AMD提供切实可靠的科学依据。

年龄相关性黄斑变性(AMD) 是50 岁以上人群视力丧失的主要病因，其发病机制尚未完全阐明。最近研究发现AMD发生与miRNA引起的表观遗传改变有关，其中miRNA-23a和氧化应激反应关系密切，后者是AMD发病的重要诱因，揭示miRNA调控AMD发生的分子机制将为AMD防治提供新靶点。杞灵颗粒是我们临床多年治疗AMD的经验方，前期研究发现可以保护视网膜氧化应激损伤，杞灵颗粒的抗氧化作用是否是通过逆转氧化应激因素导致的miRNA-23a异常改变而实现值得进一步探讨。本项目以可见光联合烟雾中主要成分氢醌为氧化应激因素诱导AMD动物模型，采用细胞分子生物学、病理学等现代研究技术，从Fas/FasL和Nrf2 /Keap1 /ARE两个信号通路深入探讨了miRNA-23a调控AMD发生的分子机制及杞灵颗粒的干预作用。研究发现慢性光照联合氢醌饲料喂养的小鼠接近人AMD的发病进程及特点，miRNA-23a对Fas/FasL和Nrf2 /Keap1 /ARE具有不同程度的调控作用，杞灵颗粒可以改善模型小鼠视网膜功能，减少视网膜细胞的凋亡，延缓AMD的发生和进展，其机制可能是通过对Nrf2 /Keap1、Fas/FasL通路调控有关。本项目的实施为AMD的研究建立了一个新的动物模型，阐释了杞灵颗粒的作用机制，为临床防治AMD提供新思路和科学依据。