Mean ± SD tear TPC and TNF-α concentrations for normal were 7.10 ± 1.53 and 1.39 ± 0.24 pg/mL; for diabetes without retinopathy, 6.37 ± 1.65 and 1.53 ± 0.27 pg/mL; for mild NPDR, 6.32 ± 2.05 and 1.60 ± 0.21 pg/mL; for moderate NPDR, 3.88 ± 1.38 and 1.99 ± 0.05 pg/mL; and for severe NPDR, 3.64 ± 1.26 and 2.21 ± 0.04 pg/mL, respectively.
Our dissection of the mechanistic linkage between morphine and retinopathy revealed a complex interplay among morphine engagement with its μ opioid receptor (MOR) on retinal endothelial cells (RECs); morphine-induced production of tumor necrosis factor α and interleukin-6 (IL-6), causing increased expression of both MOR and vascular endothelial growth factor receptor 2 (VEGFR2) on RECs; morphine/MOR engagement transactivating VEGFR2; and convergence of MOR, VEGFR2, and IL-6 activation on JAK/STAT3-dependent REC proliferation and angiogenesis.
At 12 weeks after fenofibrate treatment, serum IL-1β, TNF-α, VEGF, and Lp-PLA2 levels were detected.In PDR and NPDR patients, levels of serum cytokines such as IL-1β (120.56 ± 27.32 pg/mL vs 112.34 ± 19.45 pg/mL vs 82.9 ± 13.8 pg/mL), TNF-α (125.86 ± 25.57 pg/mL vs 109.48 ± 20.15 pg/mL vs 80.7 ± 12.8 pg/mL), VEGF (166.65 ± 37.74 pg/mL vs 148.54 ± 36.27 pg/mL vs 88.97 ± 24.86 pg/mL), and Lp-PLA2 (172.34 ± 45.22 μg/L vs 154.66 ± 40.98 μg/L vs 125.88 ± 38.87 μg/L) were significantly higher than in diabetes patients without retinopathy.
Together, these studies show a clear role for NFAT-signaling in TNFα-induced retinal leukostasis, and identify NFATc2 and NFATc4 as potentially valuable therapeutic targets for treating retinopathies in which TNFα plays a pathogenic role.
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor inducible-14 (Fn14), have been implicated in angiogenesis, but their role in retinal diseases is unknown.
The release of TNF-alpha from diabetic cells correlated negatively with serum levels of apolipoprotein B (apoB) (R = -0.755, P = 0.001), total plasma cholesterol (R = - 0.702, P = 0.002) and the presence of retinopathy (R = -0.572, P = 0.021).
In this study, we correlated the length of the (GT)n microsatellite di-nucleotide repeat upstream to the promoter region of TNF gene with susceptibility for the development of retinopathy.