TITLE

Effect of the blockade of the IL-23-Th17-IL-17A pathway on streptozotocin-induced diabetic retinopathy in rats

AUTHOR(S)
Xu, Haiyan; Cai, Min; Zhang, Xuedong
PUB. DATE
September 2015
SOURCE
Graefe's Archive of Clinical & Experimental Ophthalmology;Sep2015, Vol. 253 Issue 9, p1485
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Purpose: 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-17ACD4 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-17ACD4 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.
ACCESSION #
109077626

 

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