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TLR7 deficiency contributes to attenuated diabetic retinopathy via inhibition of inflammatory response.
Biochem Biophys Res Commun. 2017 11 18; 493(2):1136-1142.BB

Abstract

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-α (TNF-α), interleukin (IL)-1β, IL-6, IL-18 and IL-12, was highly reduced by TLR7-deficiency in DR mice. Consistently, WT/DR mice exhibited higher phosphorylation of IκB kinase α (IKKα), inhibitor of NF-κB α (IκBα) and nuclear factor κB (NF-κB), 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-κB 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.

Authors+Show Affiliations

Department of Ophthalmology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No.107, Yanjiang West Road, Guangzhou, Guangdong 510000, China.Department of Ophthalmology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No.107, Yanjiang West Road, Guangzhou, Guangdong 510000, China.Department of Ophthalmology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No.107, Yanjiang West Road, Guangzhou, Guangdong 510000, China.Department of Ophthalmology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No.107, Yanjiang West Road, Guangzhou, Guangdong 510000, China. Electronic address: 1757107852@qq.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28843858

Citation

Liao, Yun-Ru, et al. "TLR7 Deficiency Contributes to Attenuated Diabetic Retinopathy Via Inhibition of Inflammatory Response." Biochemical and Biophysical Research Communications, vol. 493, no. 2, 2017, pp. 1136-1142.
Liao YR, Li ZJ, Zeng P, et al. TLR7 deficiency contributes to attenuated diabetic retinopathy via inhibition of inflammatory response. Biochem Biophys Res Commun. 2017;493(2):1136-1142.
Liao, Y. R., Li, Z. J., Zeng, P., & Lan, Y. Q. (2017). TLR7 deficiency contributes to attenuated diabetic retinopathy via inhibition of inflammatory response. Biochemical and Biophysical Research Communications, 493(2), 1136-1142. https://doi.org/10.1016/j.bbrc.2017.08.085
Liao YR, et al. TLR7 Deficiency Contributes to Attenuated Diabetic Retinopathy Via Inhibition of Inflammatory Response. Biochem Biophys Res Commun. 2017 11 18;493(2):1136-1142. PubMed PMID: 28843858.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TLR7 deficiency contributes to attenuated diabetic retinopathy via inhibition of inflammatory response. AU - Liao,Yun-Ru, AU - Li,Zi-Jing, AU - Zeng,Peng, AU - Lan,Yu-Qing, Y1 - 2017/08/24/ PY - 2017/08/08/received PY - 2017/08/22/accepted PY - 2017/8/28/pubmed PY - 2017/10/24/medline PY - 2017/8/28/entrez KW - Diabetic retinopathy KW - Inflammation KW - MAPKs KW - NF-κB KW - TLR7 SP - 1136 EP - 1142 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 493 IS - 2 N2 - 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-α (TNF-α), interleukin (IL)-1β, IL-6, IL-18 and IL-12, was highly reduced by TLR7-deficiency in DR mice. Consistently, WT/DR mice exhibited higher phosphorylation of IκB kinase α (IKKα), inhibitor of NF-κB α (IκBα) and nuclear factor κB (NF-κB), 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-κB 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. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/28843858/TLR7_deficiency_contributes_to_attenuated_diabetic_retinopathy_via_inhibition_of_inflammatory_response_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(17)31644-3 DB - PRIME DP - Unbound Medicine ER -