| First Author | Liao YR | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 493 |
| Issue | 2 | Pages | 1136-1142 |
| PubMed ID | 28843858 | Mgi Jnum | J:251169 |
| Mgi Id | MGI:6103075 | Doi | 10.1016/j.bbrc.2017.08.085 |
| Citation | Liao YR, et al. (2017) TLR7 deficiency contributes to attenuated diabetic retinopathy via inhibition of inflammatory response. Biochem Biophys Res Commun 493(2):1136-1142 |
| abstractText | Diabetic retinopathy (DR) is a major microvascular complication of diabetes, resulting in neuronal dysfunction, retinal vascular leakage, and apoptosis within the retina. Innate immunity plays an important role in the pathogenesis of type 2 diabetes (T2D) and related complications. The toll-like receptors (TLRs), central to innate immunity, are essential participants in the progression and pathogenesis of the disease and its complications. In the study, streptozotocin (STZ) was combined with whole-body hypoxia for quicker induction of early-stage diabetic retinopathy (DR) in the wild type (WT) and TLR7-knockout (KO) C57BL/6 mice. The effects of TLR7 were also investigated in fructose-treated retinal pigment epithelial (RPE) cells. In the retinas of WT/DR mice, abnormal a-wave and b-wave activity, hyperfluorescence, and reduced retinal thickness were observed. DR development was associated with enhanced TLR7 expression, whose deletion dramatically reduced VEGF expression levels. And the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-18 and IL-12, was highly reduced by TLR7-deficiency in DR mice. Consistently, WT/DR mice exhibited higher phosphorylation of IkappaB kinase alpha (IKKalpha), inhibitor of NF-kappaB alpha (IkappaBalpha) and nuclear factor kappaB (NF-kappaB), which were found to be down-regulated in KO/DR mice. Similarly, DR-induced mitogen-activated protein kinases (MAPKs) activation was blocked by TLR7-knockout. In vitro, fructose incubation-triggered inflammation was reversed by TLR7 knockdown, accompanied with inactivated NF-kappaB and MAPKs pathways. And reduced reactive oxygen species (ROS) generation was observed in TLR7-knockdown cells with fructose treatment. Together, inhibiting TLR7 suppressed diabetic retinopathy by reducing inflammation and suggested a potential application in clinics. |
