葡萄膜炎基因治疗的研究进展

Recent advances in gene therapy of uveitis

葡萄膜炎是一类常见的致盲性眼病，其病因复杂、病程长、易反复，是眼科难治疾病之一。长期全身应用传统的治疗药物，如糖皮质激素和免疫抑制剂有较大的毒副作用。因此，寻找效果可靠、作用时间长的治疗方法成为必然。近年来，病毒载体介导的基因治疗在葡萄膜炎的研究中取得较大进展。目前主要通过两种方式达到治疗实验性葡萄膜炎的目的：一是利用病毒载体转导免疫调节分子，如白细胞介素（IL）-10、IL-1Ra、IL-4、IFN-α、IL-27p28在眼局部发挥免疫调节作用；二是通过载体导入与葡萄膜炎发生相关的抗原诱导免疫耐受。基因治疗葡萄膜炎有局部用药、长效和全身不良反应小的优势，可能会成为临床治疗葡萄膜炎的一种重要方法。

Uveitis is a group of common eye disease and is one of the major causes of blindness worldwide. Corticosteroids and immunosuppressive agents are commonly used for the treatment of uveitis. However,long-term application of these drugs frequently lead to numerous side effects. Recently, with the development of gene transfer techniques, viral vector mediated gene therapy has achieved remarkable success in experimental uveitis. Inhibition of ocular inflammation in animal models is obtained mainly by two ways ： first, increase of the expression of different immune modulators including IL-10, IL-1Ra, IL-4 and IFN-alpha, or IL-27p28 ; secondly, induction of immune tolerance by transferring uveitis related antigens via viral vectors. Uveitis is characterized by long-lasting and recurrent, the unique properties of local administration,long-term effectiveness and minor side effects of gene therapy may provide a noveX strategy for the treatment of the devastating uveitis.