低温环境下lncRNA甲基化对干眼免疫性炎症的影响及其调控机制

干眼是最常见的眼表疾病，发病因素复杂，免疫性炎症是其发生发展的核心病理机制。我们在临床工作中发现，东北地区冬季的低温环境对干眼的临床表现与治疗效果影响很大，提示低温是干眼的重要影响因素，但具体调控机制不清。本课题组前期研究证实非编码RNA在干眼中发挥重要的调控作用，且低温可引起lncRNA及其甲基化修饰的改变。本项目将应用lncRNA&mRNA m6A芯片结合生物信息方法，分别在低温细胞模型与干眼动物模型以及干眼患者中筛选低温环境下影响干眼的lncRNA及其相应的甲基化水平；并观察将lncRNA和甲基化相关酶敲除或过表达后，是否可以逆转由低温导致的眼表临床及免疫指标的改变，以明确此侯选的lncRNA及其相应的甲基化水平对于干眼免疫性炎症的影响及其调控机制。最终阐明低温通过非编码RNA的表观遗传学改变调控干眼免疫性炎症的具体机制，为寒地干眼的发病机制进行补充，并为治疗提供新的科学依据及靶点。

Previous studies of our group confirmed that non-coding RNA also plays an important regulatory role in dry eye. We found that the low temperature environment in winter in Northeast China has a great influence on the clinical manifestations and therapeutic effects of the disease. We also found that LncRNA and its methylation may regulate the immune inflammation of dry eye caused by low temperature, but the specific regulatory mechanism is not clear. In this study, lncRNA&mRNA m6A chips will be used in combination with bioinformatics to screen lncRNAs and its corresponding methylation level in hypothermic cell model, dry eye animal model and dry eye patients, respectively. We will also find out whether the clinical and immune changes of ocular surface caused by low temperature will be reversed after knockout or overexpression of lncRNA and methylated related enzymes, so as to clarify the effect of the candidate lncRNA and its corresponding methylation level on dry eye immune inflammation and its regulatory mechanism. Finally, the specific mechanism of regulating the immune inflammatory response of dry eye through the epigenetic change of non-coding RNA caused by low temperature is clarified, which can supplement the pathogenesis of dry eye in cold area and provide a new scientific basis and target for its treatment.