程序性死亡蛋白1（PD-1）通过介导激活诱导的细胞凋亡参与增殖性糖尿病视网膜病变的发生发展。
Programmed Death 1 (PD-1) is involved in the development of proliferative diabetic retinopathy by mediating activation-induced apoptosis.
作者信息
Fang Mengyuan, Meng Qianli, Guo Haike, Wang Liya, Zhao Zhaoxia, Zhang Liang, Kuang Jian, Cui Ying, Mai Liping, Zhu Jiening
机构信息
Southern Medical University, Guangzhou, China ; Guangdong Eye Institute, Department of Ophthalmology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Guangdong Eye Institute, Department of Ophthalmology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
出版信息
Mol Vis. 2015 Aug 21;21:901-10. eCollection 2015.
PURPOSE
Recent studies revealed that immunological mechanisms play a prominent role in the pathogenesis of proliferative diabetic retinopathy (PDR). Given the importance of the immune response in PDR and the significance of the programmed death 1 (PD-1) pathway as an immune regulatory pathway, the aim of this study is to determine the expression and functional characteristics of the PD-1 pathway in peripheral blood lymphocytes from patients with PDR.
METHODS
Peripheral blood lymphocytes were obtained from patients with PDR, age-matched patients with diabetes mellitus and no diabetic retinopathy (DM-NDR), and controls. The mRNA expression of PD-1 and its ligands were determined using real-time PCR. The frequencies of PD-1 and its ligands, activation-induced apoptosis, IFN-γ, and IL-4 were determined by flow cytometry.
RESULTS
The PD-1 mRNA expression markedly decreased, while the frequency of PD-1(+) cells increased in the PDR group compared with the DM-NDR and control groups. The expression of PD-ligand 1 (PD-L1) mRNA and PD-L1(+) cells in the PDR group was lower than that in the other two groups. In the PDR group, the frequency of Annexin V(+)PI(-) and Annexin V(+)PI(-)PD-1(+) cells increased, while the frequency of Annexin V(+)PI(-)PD-L1(+) cells decreased. Although their expression was upregulated, the ratio of PD-1(+) IFN-γ(+) to PD-1(+)IL-4(+) cells in the PDR group was not significantly different to that in the DM-NDR and control groups.
CONCLUSIONS
These results suggest that PD-1 is involved in the development of PDR by mediating activation-induced apoptosis.
目的
近期研究表明，免疫机制在增殖性糖尿病视网膜病变（PDR）的发病机制中起重要作用。鉴于免疫反应在PDR中的重要性以及程序性死亡1（PD-1）通路作为一种免疫调节通路的意义，本研究旨在确定PDR患者外周血淋巴细胞中PD-1通路的表达及功能特征。
方法
从PDR患者、年龄匹配的糖尿病但无糖尿病视网膜病变（DM-NDR）患者以及对照组获取外周血淋巴细胞。使用实时PCR测定PD-1及其配体的mRNA表达。通过流式细胞术测定PD-1及其配体的频率、活化诱导的凋亡、IFN-γ和IL-4。
结果
与DM-NDR组和对照组相比，PDR组中PD-1 mRNA表达显著降低，而PD-1(+)细胞频率增加。PDR组中PD配体1（PD-L1）mRNA和PD-L1(+)细胞的表达低于其他两组。在PDR组中，膜联蛋白V(+)碘化丙啶(-)和膜联蛋白V(+)碘化丙啶(-)PD-1(+)细胞的频率增加，而膜联蛋白V(+)碘化丙啶(-)PD-L1(+)细胞的频率降低。尽管其表达上调，但PDR组中PD-1(+)IFN-γ(+)与PD-1(+)IL-4(+)细胞的比例与DM-NDR组和对照组相比无显著差异。
结论
这些结果表明，PD-1通过介导活化诱导的凋亡参与PDR的发生发展。
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