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Bo Lei, Ru Lin; Attenuation of Intraocular Inflammatory Responses in Experimental Autoimmune Uveitis by TMP Is Associated with Modulating of the STAT3 and STAT4 Pathways. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5328.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the protective effect of tetramethylpyrazine (TMP) on retinal inflammation in experimental autoimmune uveitis (EAU) mice and to explore the underlying mechanism.
B10.RIII mice were subcutaneous injected by IRBP peptide with CFA to induce EAU. TMP (50 mg/kg/d) or vehicle was administrated intraperitoneally starting from day 2 before to day 14 after IRBP peptide immunization as the prevention phase, and from day 8 to day 14 as the effector phase, respectively. The clinical and histological scores were used to evaluate the severity of ocular inflammation in EAU mouse eyes. The pro-inflammatory cytokines IL-6, TNF-α, IL-1β, MCP-1, anti-inflammatory cytokine IL-10, Th1 cell signature cytokine IFN-γ and Th17 cell signature cytokine IL-17 were detected by real-time PCR. Retinal function was assessed by dark- and light-adapted ERG. The protein levels of p-STAT3 and p-STAT4 were detected by Western blotting.
In the prevention and effector phases, the clinical and histological scores were remarkable reduced in the EAU mice treated with TMP systemically. Intraperitoneally administration of TMP significantly decreased the retinal mRNA expression of IL-6, TNF-α, IL-1β, MCP-1, IFN-γ and IL-17, but significantly enhanced the expression of IL-10 in EAU mice. Compared with the vehicle treated EAU group, the ERG b- and a-wave amplitudes were alleviated in the TMP treated EAU eyes. Meanwhile, TMP significantly preserved the expression of p-STAT3 and p-STAT4 at protein levels.
We found systemic administration of TMP significantly reduced ocular inflammation and retinal function impairment in both prevention and effector phases in EAU mice. Our results suggested the anti-inflammatory effect of TMP was associated with inhibition of the immune responses and the STAT3 and STAT4 signaling.
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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