青光眼是严重的致盲性眼病。前期工作证实CD4+T细胞亚群失衡在青光眼视神经损伤中作用重要。调节型T细胞（Tregs）是机体内最重要的免疫调节细胞，在多种神经系统病变中具保护作用。前期发现青光眼患者体内Tregs的特征性转录因子FOXP3高甲基化并伴细胞表型异常。已知FOXP3基因的保守非编码序列（CNS）区域甲基化异常是导致Tregs功能失活的关键。由此提出：CNS区域甲基化修饰调控Tregs的功能异常可能在青光眼视神经损伤中具关键作用。本课题拟全面检测Tregs亚群在高眼压小鼠模型中的谱系分布特点，并检测FOXP3基因的CNS区域甲基化水平与视神经损伤之间的关系；通过CRISPR-dCas9基因编辑工具联合甲基化调控蛋白酶（Tet1及DNMT3a）靶向干预CNS区域甲基化水平，研究其变化对Tregs功能活性的影响，以及对青光眼视神经免疫损伤的干预作用。期望为青光眼视神经保护提出新靶点。

Glaucoma is a serious blinding eye disease. Previous work has confirmed that the imbalance of CD4 + T cell subsets plays an important role in glaucoma optic nerve injury. Regulatory T cells (Tregs) are the most important immune regulatory cells in the body and play a protective role in many neurological diseases. Previously, high methylation of FOXP3, a characteristic transcription factor of Tregs, was found in glaucoma patients with abnormal cell phenotype. Abnormal methylation in the conserved non-coding sequence (CNS) region of FOXP3 gene is the key to Tregs dysfunction. It is suggested that the dysfunction of Tregs regulated by methylation modification in CNS may play a key role in glaucoma optic nerve injury. In this study, we intend to comprehensively detect the pedigree distribution of Tregs subgroup in high intraocular pressure mice model and the relationship between the methylation level of CNS region of FOXP3 gene and optic nerve injury; target intervention of methylation level in CNS region by CRISPR-dCas9 gene editing tool combined with methylation-regulated protease (Tet1 and DNMT3a), and study the effect of its changes on Tregs functional activity, as well as the relationship between FOXP3 gene methylation level and optic nerve injury. Intervention effect on glaucoma optic nerve immune injury. It is expected that a new target for glaucoma optic nerve protection will be proposed.