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

  • Retinal Disorders
  • Published:
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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.

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Acknowledgments

All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest, and none were reported. This study was conducted with the approval of the Ethics Committee of Chongqing Medical University. The work was supported by the Health Bureau Foundation of Chongqing Project (2011-1-029) and a National Natural Science Foundation Project Grant (81371843). X.D Zhang and H.Y Xu were involved in the design and conduct of the study; H.Y Xu, M Cai, and C.K Wang were involved in the collection, management, analysis, and interpretation of the data.

Conflict of Interest

None declared.

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Authors and Affiliations

  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

    Haiyan Xu, Min Cai & Xuedong Zhang

  2. Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, People’s Republic of China

    Haiyan Xu, Min Cai & Xuedong Zhang

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  1. Haiyan Xu
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  2. Min Cai
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Correspondence to Xuedong Zhang.

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Xu, H., Cai, M. & Zhang, X. Effect of the blockade of the IL-23-Th17-IL-17A pathway on streptozotocin-induced diabetic retinopathy in rats. Graefes Arch Clin Exp Ophthalmol 253, 1485–1492 (2015). https://doi.org/10.1007/s00417-014-2842-9

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  • DOI: https://doi.org/10.1007/s00417-014-2842-9

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