July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
IL-17 exacerbates diabetic retinopthy through a novel mechanism of M1 microglia polarization
Author Affiliations & Notes
  • Chang He
    Sun Yat-sen University, Guangzhou, China
  • Footnotes
    Commercial Relationships   Chang He, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3561. doi:
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      Chang He; IL-17 exacerbates diabetic retinopthy through a novel mechanism of M1 microglia polarization
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):3561.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Diabetic retinopathy (DR) is recognized as a chronic inflammatory disease but the involved inflammatory mechanism remains unclear. Interleukin 17 (IL-17) is implicated in various inflammatory diseases and its potential role and mechanism in DR needs to be further clarified.

Methods : DR mice were established by streptozotocin (STZ) injection for 5 consecutive days and received intravitreal injection of IL-17 Nab, IL-17, IL-6 Nab, S3I-201(STAT3 inhibitor) or IgG ten weeks after STZ induction, respectively. The diabetic retinopathy was monitored by Evans blue assay, vascular leukostasis assay, and Tunel assay. The microglia phenotype and related genes expression were evaluated by immunofluorescent staining, qPCR, and Western blot analysis.

Results : IL-17 was elevated significantly in the retina of STZ-induced DR mice and IL-17 blockade using neutralizing antibody prevented vascular leakage and leukostasis, the inflammatory pathology of DR. Mechanistically, IL-17 induced a M1- microglia phenotype exhibiting iNOS+Iba-1+. IL-17-dependent activation of the STAT3-iNOS pathway was essentially required for the M1-microglia polarization, which led to high levels of IL-6 production. Blocking IL-6 attenuated IL-17-induced vascular leakage and leukostasis.

Conclusions : Our data provide novel mechanistic insights on IL-17-induced DR. IL-17 serves as a critical instigator cytokine to shift microglia toward the pro-inflammatory M1 phenotype via STAT3 activation and promoting IL-6 generation, orchestrating the inflammatory microenvironment of DR.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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