Therapeutic Effect Of Eye Drops Containing A Mixture Of Perilla Extract And Hyaluronic Acid In A Mouse Model Of Experimental Dry Eye

Objective:To investigate the therapeutic effects of topicalapplication of perilla extract and hyaluronic acid(HA)mixtures in a mouse model of experimental dry eye(EDE).Methods:In this study,mice were randomly divided into 6 groups:(1)untreated control(UT),not exposed to desiccating stress or treated topically;(2)EDE control,exposed to desiccating stress,however,receiving no eye drops;(3)HA control,EDE mice treated with HA;(4)EDE mice treated with 0.1%perilla extract alone;(5)EDE mice treated with 0.01%perilla extract and 0.1%HA mixture,and(6)EDE mice treated with 0.1%perilla extract and 0.1%HA mixture.Each group consists of 10 animals.All treatment groups received 2μL of eye drops four times a day.Corneal irregularity scores,tear secretion,tear film break-up time(TBUT),corneal fluorescien staining scores,ROS,and conjunctival goblet cells were measured at 10 days after treatment.In addition,Levels of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-a,and interferon(IFN)-y were measured in the conjunctiva at 10 days using a multiplex immunobead assay.The concentrations of hexanoyl-lys(HEL)and 4-hydroxynonenal(4-HNE)in conjunctiva tissue were measured with enzyme-linked immunosorbent assays.Results:Compared to the EDE groups,the mice treated with topical application of the 0.1%perilla extract and 0.1%HA mixture showed significant improvements in all clinical parameters,Corneal irregularity scores,tear secretion,tear film break-up time(TBUT),corneal fluorescien staining scores,IL-1β,IL-6,TNF-α,and IFN-γlevels,goblet cell density,number of 4-HNE-positive cells,and extracellular ROS production(P<0.001).Conclusion:Topically applied eye drops containing a mixture of 0.1%perilla extract and 0.1%HA could improve corneal irregularity and corneal epithelial barrier disruption,and decrease inflammatory cytokines and oxidative stress markers on the ocular surface.Topical 0.1%perilla extract and 0.1%HA mixture may have a greater therapeutic effect on clinical signs and inflammation of dry eye compared with HA artificial tears.