Topical Application Of Paeonol Ameliorates Inflammatory Response In Experimental Dry Eye Model Via Modulating NF-?B Pathway

Purpose:To investigate the role of paeonol,a novel compound isolated from Chinese herb,in ocular surface damage of dry eye.Methods:Topical applications of paeonol or vehicle were performed in the mice subjected to desiccating stress(DS).The phenol red cotton test was used to measure tear production,and Oregon green dextran staining was performed to assess corneal epithelial barrier function.PAS staining was used to quantify conjunctival goblet cells.Immunofluorescent staining,western blot and real-time quantitative RT-PCR were conducted to detect the expression of matrix metalloproteinase(MMP)-3 and-9 in corneal epithelium.Apoptosis of ocular surface was assessed by TUNEL staining,,immunofluorescent staining and western blot of the activation of caspase-3 and-8.Inflammation was evaluated by CD4+T-cell infiltration and production of T helper(Th)cytokines,including IL-13,IL-17A,IFN-y and TNF-a in conjunctiva.The total and phosphorylated NF-?B in conjunctiva were detected by Western blot.Results:Compared with vehicle control mice,paeonol-treated mice showed increased tear production,decreased goblet cell loss,and improved corneal barrier function.Topical paeonol decreased the expression of MMP-3 and-9 in corneal epithelium,and suppressed cell apoptosis in ocular surface under DS.Meanwhile,topical paeonol reduced CD4+T-cell infiltration,with decreased production of IFN-?,TNF-a and IL-17A and increased production of IL-13 in conjunctiva.Paeonol-treated group down-regulated NF-?B signaling pathway activated in experimental dry eye model.Conclusions:Topical application of Paeonol effectively alleviated ocular surface damage via modulating NF-?B Pathway to suppress cell apoptosis and CD4+T-cell-mediated inflammation in ocular surface of dry eye.