title: Toll-like receptor (TLR)-2/4 expression in retinal ganglion cells in a high-glucose environment and its implications.
abstract: Diabetic retinopathy (DR), a major complication of diabetes mellitus, is the leading cause of adult blindness. The Toll-like receptor (TLR) family is believed to be involved in the pathogenesis and progression of DR. Here, we investigated the expression profiles of TLR-2 and TLR-4 in retinal ganglion cells (RGCs), in an attempt to elucidate the role of these molecules in the etiology of DR. In vitro cultured RGCs were divided into control and high-glucose groups. The mRNA and protein levels of TLR-2, TLR-4, and nuclear factor (NF)-κB were detected by real-time PCR and western blotting. RGCs were further transfected with specific siRNA targeting TLR2/TLR4; the proliferation of transfected RGCs and their tumor necrosis factor (TNF)-α and interleukin (IL)-8 secretory capacity were analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and enzyme-linked immunosorbent assays (ELISA), respectively. In a high-glucose environment, TLR-2/4 expression was significantly upregulated in RGCs (while their viability decreased); additionally, NF-κB expression and secretion of TNF-α and IL-8 were significantly increased. Co-silencing of the TLR-2 and TLR-4 genes inhibited NF- κB expression and TNF-α/IL-8 secretion, while increasing the survival rate of RGCs. Therefore, a high-glucose environment can potentiate the expression of TLR-2 and TLR-4 in RGCs, activate the downstream signaling pathway, and increase the secretion of pro-inflammatory factors, thereby aggravating DR.
authors.affiliation: Department of Ophthalmology, The Second People's Hospital of Liaocheng City, Linqing, Shandong Province, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of ICU, The Second People's Hospital of Liaocheng City, Linqing, Shandong Province, China.
authors.forename: C H
authors.initials: CH
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, The Second People's Hospital of Liaocheng City, Linqing, Shandong Province, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Liu
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics / Q000473:pathology; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose