title: Blocking IL-17A Alleviates Diabetic Retinopathy in Rodents.
abstract: OBJECTIVE
  Interleukin (IL)-17A, a proinflammatory cytokine, has been implicated in several autoimmune diseases. However, it is unclear whether IL-17A is involved in diabetic retinopathy (DR), one of the most serious complications of autoimmune diabetes. This study aimed to demonstrate that IL-17A exacerbates DR by affecting retinal Müller cell function.
  
  
  METHODS
  High glucose (HG)-treated rat Müller cell line (rMC-1) was exposed to IL-17A, anti-IL-17A-neutralizing monoclonal antibody (mAb) or/and anti-IL-17 receptor (R)A-neutralizing mAb for 24 h. For in vivo study, DR was induced by intraperitoneal injections of streptozotocin (STZ). DR model mice were treated with anti-IL-17A mAb or anti-IL-17RA mAb in the vitreous cavity. Mice that were prepared for retinal angiography were sacrificed two weeks after intravitreal injection, while the rest were sacrificed two days after intravitreal injection.
  
  
  RESULTS
  IL-17A production and IL-17RA expression were increased in both HG-treated rMC-1 and DR retina. HG induced rMC-1 activation and dysfunction, as determined by the increased GFAP, VEGF and glutamate levels as well as the downregulated GS and EAAT1 expression. IL-17A exacerbated the HG-induced rMC-1 functional disorders, whereas either anti-IL-17A mAb or anti-IL-17RA mAb alleviated the HG-induced rMC-1 disorders. Intravitreal injections with anti-IL-17A mAb or anti-IL-17RA mAb in DR model mice reduced Müller cell dysfunction, vascular leukostasis, vascular leakage, tight junction protein downregulation and ganglion cell apoptosis in the retina.
  
  
  CONCLUSIONS
  IL-17A aggravates DR-like pathology at least partly by impairing retinal Müller cell function. Blocking IL-17A is a potential therapeutic strategy for DR.
authors.forename: Ao-Wang
authors.initials: AW
authors.lastname: Qiu
authors.forename: Qing-Huai
authors.initials: QH
authors.lastname: Liu
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D063928:Ependymoglial Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000276:immunology; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000276:immunology; D007116:Immunization, Passive; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D058449:Intravitreal Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053722:Receptors, Interleukin-17 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D012160:Retina / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D027341:Excitatory Amino Acid Transporter 1; D005904:Glial Fibrillary Acidic Protein; C098680:Il17a protein, mouse; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; C493393:Slc1a3 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C528900:glial fibrillary astrocytic protein, mouse; C467480:vascular endothelial growth factor A, mouse; D013311:Streptozocin; D005974:Glutamate-Ammonia Ligase
keywords: Diabetic retinopathy; Interleukin-17 receptor A; Interleukin-17A; Retinal Müller cells