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Xiaoqing Chen, Dan Liang; Doxycycline Suppresses Ocular Inflammation by Stat3/MiR155/Th17 Pathway. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2539. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Uveitis is catastrophic intraocular inflammation and contributing to over 10% blindness in China.Current therapeutics for uveitis are mainly corticosteroids and immunosuppressive agents, and good efficacy has been achived in most patients. However, high costs and long term adverse complications are unneglectable.Novel and effective treatment are desirable. As a broad spectrum and long acting antibiotic, Doxycycline has been used safely in clinics for the past decades. Recently, anti-inflammation and immunosuppressive effect of Doxycycline are attracting researcher’ eyes. Doxycycline has been used to attenuate rheumatoid arthritis, rosacea, periodontitis and other autoimmune diseases. In this study, we aim to investigate the effect of Doxycycline on experimental autoimmune uveitis(EAU) and potential mechanisms.
We induced EAU in C57BL/6 mice by immunization with interphotoreceptor retinoid-binding protein in complete Freund's adjuvant. Mice were gavaged Doxycycline 5mg/kg daily from Day 7 until Day 21. Disease severity was assessed by fundoscopy and histological examination. The development of inflammation or production of inflammatory molecules was assessed by flow cytometry and ELISA and mRNA analysis of cells in the draining lymph nodes and retina.
Treatment with doxycycline significantly reduced the clinical and pathological scores of EAU (P <0.001), with significant decreases in inflammatory cell infiltration, protein concentrations, and the production of IL17A, TNFα, and IL6 in the draining lymph nodes and retina. In vitro, doxycycline significantly inhibited IRBP specific Th17 induction and IL17A production dependent on Stat3/miR155/Th17 pathway. Importantly, Doxycycline also suppresses systemic immune responses.
Oral administration of Doxycycline attenuated uveitis in the mouse EAU model by suppressing the expansion of pathogenic cells and migration into the retina. Stat3/miR155/Th17 pathway is essential for the anti-inflammatory and immunoregulatory effect of Doxycycline. Doxycycline is safe and effective, suggesting that oral administration of Doxycycline can be exploited as an alternative choice for human uveitis.
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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