title: Programmed Death 1 (PD-1) is involved in the development of proliferative diabetic retinopathy by mediating activation-induced apoptosis.
abstract: OBJECTIVE
  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.
authors: Southern Medical University, Guangzhou, China ; Guangdong Eye Institute, Department of Ophthalmology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Mengyuan
authors: M
authors: Fang
authors: Guangdong Eye Institute, Department of Ophthalmology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Qianli
authors: Q
authors: Meng
authors: Guangdong Eye Institute, Department of Ophthalmology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Haike
authors: H
authors: Guo
authors: Henan Eye Institute, Henan Eye Hospital, Zhengzhou, China.
authors: Liya
authors: L
authors: Wang
authors: Henan Eye Institute, Henan Eye Hospital, Zhengzhou, China.
authors: Zhaoxia
authors: Z
authors: Zhao
authors: Guangdong Eye Institute, Department of Ophthalmology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Liang
authors: L
authors: Zhang
authors: Department of endocrinology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Jian
authors: J
authors: Kuang
authors: Guangdong Eye Institute, Department of Ophthalmology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Ying
authors: Y
authors: Cui
authors: Research Center of Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Liping
authors: L
authors: Mai
authors: Research Center of Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Jiening
authors: J
authors: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D003930:Diabetic Retinopathy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D008024:Ligands; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger