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MINGLI QU, Xia Qi, Qian Wang, Lei Wan, Qingjun Zhou; Therapeutic effect of STAT3 inhibition on experimental murine dry eye.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):290.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of signal transducer and activator of transcription-3 (STAT3) activation in the ocular surface damage of dry eye in mice.
Benzalkonium chloride (BAC)-induced Balb/c mice and Tabby (lack meibomian gland) mice were used as dry eye models. The expression of phosphorylated STAT3 (p-STAT3) were detected by Western blot and immunofluorescent staining. STAT3 inhibition was performed by topical application of STAT3 inhibitor (S31-201) or vehicle control. Tear production was measured by phenol red cotton test. Corneal barrier function was assessed by fluorescein sodium staining. The density of conjunctival goblet cells was quantified by PAS staining. The expression of MMP-9, keratin10, activated caspase-8, TUNEL and inflammation cytokines in ocular surface were detected by immunofluorescent staining, PCR and ELISA assays. The therapeutic effect of S31-201 was compared with two JAK inhibitors Tofacitinib and Ruxolitinib.
Elevated expression of p-STAT3 was detected in the corneal and conjunctival epithelium of the BAC-induced and tabby mice. Topical use of STAT3 inhibitor increased the tear production, improved corneal barrier function, and elevated the density of conjunctival goblet cells. Moreover, S31-201 decreased the expression of MMP-9 and keratin10, suppressed the apoptosis of corneal and conjunctival epithelial cells, and reduced the levels of IL-1β, IL-6, IL-10, IL-23, IL-17A and TNF-α. Compared with Tofacitinib and Ruxolitinib, the STAT3 inhibitor S31-201 showed superior effects of improving tear production and reducing inflammatory cytokine expression.
Elevated STAT3 activation is involved in the pathogenesis of dry eye, while targeting STAT3 can effectively alleviate dry eye-induced ocular surface damage.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Elevated STAT3 activation in different dry eye models.
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