CD4+T细胞亚群失衡在高眼压视神经损伤中的作用

项目名称： CD4+T细胞亚群失衡在高眼压视神经损伤中的作用

项目编号： No.81200683

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 陈慧慧

作者单位： 中南大学

项目金额： 23万元

中文摘要： 青光眼是目前首位不可逆的致盲性眼病。高眼压是其病理损伤的重要启动因素，但眼压精确控制后视神经仍持续损伤，具体机制不明。自身免疫病理对中枢神经元的持续性损伤具关键作用，大量研究也指向其与青光眼病理损伤相关。前期我们已证实：以CD4+T细胞为核心的自身免疫病理对高眼压视神经的持续性损伤具重要作用。已知CD4+T细胞亚群失衡是自身免疫病理产生的关键。据此，我们推测"CD4+T细胞亚群失衡在高眼亚视神经的持续病理损伤中具重要作用"。本课题拟首先全面检测CD4+T细胞亚群在高眼压小鼠模型中的分化、分布及功能状态，其次通过回输单一亚型CD4+T细胞至T细胞免疫缺陷小鼠，明确各亚型的视神经损伤作用，最后通过阻断病理性T辅助细胞或回输保护性Treg细胞，干预其亚群的失衡机制。本课题首次在细胞及分子水平探讨高眼压的自身免疫病理，期望能进一步完善青光眼的病理损伤机制，并为临床青光眼的防治提供新思路。

中文关键词： 青光眼；T细胞；视神经；视网膜节细胞；自身免疫

英文摘要： Glaucoma is the first leading cause of unconvertible blindness diseases; high intraocular pressure is the main risk factor and therapy target. There are still plenty of patients who got fine intraocular pressure control, however their visual field keep losing. Autoimmunity reaction is the key point to the progressive degeneration of neuron in central never system. And more and more evidence have showed it also related to the optic neuropathy in glaucoma. In our preliminary work, we have proved the activation of CD4+ T cell play a very important role in the neuropathology of glaucoma mice model. First we are planning to exam the distribution and function pattern of the CD4+ T cell subsets in the glaucoma mice model, and then we are planning to transfer the single CD4+ T cell subset back to the TCKO mice to identify the specific functional role in glaucoma. At last we are planning to block the pathologic T helper cell or transfer the protective Treg cell back the wild type glaucoma mice model. We hope we can further improve the glaucoma pathology theory and raise the new therapeutic target of the clinical treatment. .

英文关键词： glaucoma；T cell；optic nerve；RGCs；autoimmunity