HIVEP3在自身免疫性葡萄膜炎中的作用及机制研究

自身免疫性葡萄膜炎是常见的致盲眼病，病程长、易反复，没有特效的根治性药物。该疾病发病机制复杂，亟需更深入的具有临床转化价值的科学研究。表观遗传修饰对机体免疫功能发挥及免疫稳态调控至关重要，DNA甲基化是其重要的类型之一，与葡萄膜炎之间的联系非常紧密。课题组前期利用全基因组甲基化芯片和mRNA测序等技术鉴定到HIVEP3基因与自身免疫性葡萄膜炎的发生有关，但其在葡萄膜炎发生发展过程中的作用及机制尚不明确，其临床转化和应用价值也有待进一步探索。本项目拟在前期基础上，进一步通过人群研究鉴定和验证HIVEP3 与葡萄膜炎的关系，并通过体外细胞实验（淋巴细胞原代培养下HIVEP3的敲减和过表达），动物模型体内试验（HIVEP3基因敲除小鼠的实验性自身免疫性葡萄膜炎模型）揭示HIVEP3在葡萄膜炎发生、发展中的作用及分子调控机制，为葡萄膜炎的诊疗提供理论指导以及新药物研发提供新的靶点。

Autoimmune uveitis is a common eye disease that can cause blindness.. It has a long duration, and is easy to recur, and also has no effective curative medicine. The pathogenesis of the disease is complex and unclear. Therefore, more in-depth scientific research with clinical translation value is urgently needed. Epigenetic modification plays a vital role in regulating the immune function and immune homeostasis. DNA methylation is one of its important epigenetics modifications. and involved in the pathogenesis of uveitis. Here, we identified that HIVEP3 gene was related to the onset of uveitis through whole genome methylation chip and mRNA sequencing analysis in the pre-experiment. However, its mechanism in the development of uveitis is still unknown and needs to be further explored. First, this project intends to further identify and verify the relationship between HIVEP3 and uveitis through population studies. Then we used in-vitro cell experiments (HIVEP3 knock-down or overexpression in primary culture of lymphocyte) and in-vivo experiments in animal models (experimental autoimmune uveitis model in HIVEP3 knocked-out mice) to reveal the role of HIVEP3 in the occurrence and development of uveitis and its molecular regulatory mechanism. Finally, we aim to provide a theoretical guidance for the diagnosis and treatment of uveitis, and also provide new targets for the development of new drugs.