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Zhijie Wang, Yong Zeng, Zekai Cui, Jiansu Chen, Shibo Tang; The involvement of circadian rhythm gene REV-ERBα in regulation of ocular inflammation. Invest. Ophthalmol. Vis. Sci. 2020;61(7):707.
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Ocular inflammation is pathological mechanism of many eye diseases. Circadian rhythm plays a vital role in inflammation and metabolism, and it is also a potent target for treatment of ocular inflammation. Here, we investigate whether the core circadian rhythm gene REV-ERVα alleviates ocular inflammation, and the relative mechanism and treatment are explored.
The study was divided into three groups in mice: blank control group, vehicle group-ocular inflammation induced by lipopolysaccharide (LPS) with injection of vehicle, treatment group-ocular inflammation treated by SR9009 (a synthetic agonist for REV-ERBα). We collected mouse retina in blank control group at multiple Zeitgeber times (ZT) of days, and analyzed the expression of circadian rhythm genes. The clinical scores and mRNA levels of inflammatory cytokines were analyzed in ocular inflammation after injection of SR9009. In addition, the microglia cell line BV2 and primary retinal microglia cells were pretreated by SR9009 and then incubated with LPS. The expression of inflammatory cytokine genes was analyzed 8 hours later.
The time-of-day oscillation in the expression of circadian rhythm genes was observed in mouse retina (Fig.1). In ocular inflammation eyes, the expression of circadian genes including BMAL1,CRY1 was decreased, while the expression of REV-ERBα was increased. The treatment of SR9009 significantly alleviated clinical signs of ocular inflammation (Fig.2), and the mRNA levels of IL-6, CCL2, IL-1β and TNFα were also decreased compared with vehicle group. In vitro, SR9009 treatment significantly suppressed LPS-induced expression of IL-6, CCL2, IL-1β in microglia cells.
The expression of circadian genes were impaired in LPS-induced ocular inflammation. REV-ERBα activation by SR9009 has a protective effect on LPS-induced ocular inflammation.
This is a 2020 ARVO Annual Meeting abstract.
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