Effect Of Topical Treatment With Antisense Oligonucleotides Targeting Tumor Necrosis Factor-α On Experimental HSV-1-induced Chorioretinitis In Mice

Objective:To investigate the effect to the pathological process of topical treatment with antisense oligonucleotides (ASON) targeting tumor necrosis factor-a (TNF-a) in experimental, herpes simplex virus type-1 (HSV-1) induced chorioretinitis of mouse eye.Methods:Fifty BALB/C mice were randomly divided into treatment group and control group (twenty-five mice for each group). The Von Szily model was induced in mice by inoculating 105 plaque-forming units (pfu) of HSV-1 (KOS strain) into anterior chamber of right eye. In treatment group, FITC-labeled ASON targeting TNF-a were injected subconjunctive of left eye on days-1,1,4. Whereas, buffer were used by the same ways on the same day in control group. The clinical appearances were observed after infection each day. The sections were stained with corresponding antibody and observed the expression of MMP-9 and CD3 The eyes were examined histologically. The TNF-a content of retina and choroids were measured by ELISA.Results:After infection, acute inflammation appeared in the right eye for both groups. As for the noninocubated eye, the inflammation in treatment group was significantly decreased than in control group. The number of inflammatory cells in treatment group was significantly lower than them in control group, especially in the place of choroids retina and ciliary body.Compared with control group,the numbers of MMP-9 and CD3 Positive cell in the place of choroid and retina were significantly reduced in experimental group. The content of TNF-a in the place of choroid and retina of the treatment group was diminished.Conclusions:The data suggested that TNF-a ASON reduced the content of TNF-a in mice eye, and this topical treatment decreased the inflammatory reaction. It may be an effective method for treating HSV-1 induced uveitis in clinic.