Haiyan Xu1, Min Cai, Xuedong Zhang. 1. 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.
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-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.
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-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.
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