miR-184在干性年龄相关性黄斑变性的发病机制研究

Age-related macular degeneration (AMD), showing an increasing incidence, has become one of the most common causes for visual impairments in people aged over 55. Dry AMD, accounting for 90% of total AMD cases, is typified by dysfunction of retinal pigment epithelium (RPE) cells; however, its concrete pathogenesis is still unclear with no efficient therapy available. MiR-184 plays an important role in maintaining the regular function of RPE cells, while its role in AMD pathogenesis is still unclear. We, herein, aim to deeply investigate the association between miR-184 defect and AMD per the following aspects: 1) Build both in vivo and in vitro AMD disease models to see the role of miR-184 defect in AMD pathogenesis; 2) Study the regulatory network of miR-184 to explore its role in the molecular pathogenesis of retinal dysfunction; 3) Investigate the safety and efficiency of miR-184 targeted treatment in multiple in vivo and in vitro models. Taken together, our study aims to study the association between miR-184 defect and AMD pathogenesis, to explore the molecular mechanism underlying RPE dysfunction generated by miR-184 defect, and to seek for safe and efficient miR-184 targeted therapy for dry AMD, thus providing novel insights into clinical treatment for AMD.

年龄相关性黄斑变性（AMD）发病率逐年升高，是我国55岁以上人群视力发生不可逆性损害的主要原因之一。干性AMD占全部AMD的90%，视网膜色素上皮层（RPE）功能障碍是其主要病因，然而其具体发病机制不清，且目前临床缺乏对其有效的治疗方式。miR-184在维持视网膜功能方面起到了极其重要的作用，然而其在AMD病程中的作用尚不明确，本研究拟从以下几个方面对miR-184在AMD疾病中的作用机制展开深入研究：1）构建干性AMD疾病模型，明确miR-184与干性AMD发病相关；2）研究miR-184相关调控网络，探索miR-184缺陷引起视网膜功能障碍的分子机制；3）在多种模型中验证和评估针对miR-184的靶向治疗的有效性和安全性。本项目旨在研究miR-184与干性AMD发病的相关性，了解其引起RPE细胞功能异常的分子机制，寻找针对miR-184的安全有效的靶向治疗，为临床治疗提供新的思路。

年龄相关性黄斑变性（AMD）发病率逐年升高，是我国55岁以上人群视力发生不可逆性损害的主要原因之一。干性AMD占全部AMD的90%，视网膜色素上皮层（RPE）功能障碍是其主要病因，然而其具体发病机制不清，且目前临床缺乏对其有效的治疗方式。本研究通过构建miR-184敲除的动物模型，发现miR-184与干性AMD发病密切相关，其通过影响RPE的分化过程，从而导致神经视网膜结构和功能破坏。通过RNA-seq,研究探索miR-184上下游调控网络并发现miR-184缺陷可能通过影响视网膜代谢参与AMD 的发病过程。最后在在体及离体模型中针对miR-184的靶向治疗的有效性和安全性进行了评估。本课题研究明确了miR-184与干性AMD发病的相关性，了解其引起RPE细胞功能异常的分子机制，并对miR-184的安全有效的靶向治疗进行评估，为临床治疗提供新的思路。