Programmed Death 1 (PD-1) is involved in the development of proliferative diabetic retinopathy by mediating activation-induced apoptosis

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.