title: Effect of the blockade of the IL-23-Th17-IL-17A pathway on streptozotocin-induced diabetic retinopathy in rats.
abstract: OBJECTIVE
  T helper 17 (Th17) cells are believed to play a critical role in the chronic inflammatory and immune response in streptozotocin (STZ)-induced retinopathy. The purpose of our study was to investigate the effect of the IL-23-Th17-IL-17A pathway via the blood-retinal barrier on STZ-induced diabetic retinopathy in rats.
  
  
  METHODS
  The ratio of IL-17A(+)CD4(+) T cells in peripheral blood mononuclear cells of STZ-treated and wild-type rats was determined using flow cytometry. The IL-17A mRNA levels in the retinas were measured using real-time PCR. The protein expression of IL-17A in the peripheral blood and retinas was measured using an ELISA kit. The retinal structure in the wild-type and STZ-treated rats was examined using hematoxylin and eosin (H&E) staining. Additionally, the permeability of the blood-retinal barrier was quantified using the Evans blue technique.
  
  
  RESULTS
  The ratio of IL-17A(+)CD4(+) T cells in peripheral blood mononuclear cells was markedly increased in rats treated with STZ compared to the wild-type group. IL-17A protein levels in the peripheral blood and retinas were also significantly elevated in STZ-treated rats. However, when the anti-IL 23Rp19 antibody was injected into the vitreous cavity in the eyes of STZ-treated rats for a period of one week, retinal pigment epithelium cells became markedly tighter, and micrangium and endothelial cells were significantly reduced. The expression of IL-17A mRNA and protein in the retina also decreased significantly compared with the placebo-treated group.
  
  
  CONCLUSIONS
  This study provided further insight into the function of the IL-23-Th17-IL-17A pathway in STZ-induced diabetic retinopathy in rats. Local injection of the anti-IL-23Rp19 antibody may improve the structure of the blood-retinal barrier, thus offering the potential for treatment using intravitreal anti-IL-23Rp19 antibodies.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, No.1 You Yi Road, Yu Zhong District, Chongqing, 400016, People's Republic of China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Cai
authors.forename: Xuedong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes; D002199:Capillary Permeability; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020381:Interleukin-17 / Q000502:physiology*; D053759:Interleukin-23 / Q000037:antagonists & inhibitors / Q000502:physiology*; D053760:Interleukin-23 Subunit p19 / Q000008:administration & dosage; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012171:Retinal Vessels / Q000502:physiology; D058504:Th17 Cells / Q000502:physiology*
chemical_list: C515934:Il17a protein, rat; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D012333:RNA, Messenger