Influence of antisense oligonucleotides targeting tumor necrosis factor-alpha on experimental herpetic-induced chorioretinitis of mouse eye.

OBJECTIVE

To investigate the effect on the pathological process of topical treatment with antisense oligonucleotides (ASON) targeting tumor necrosis factor-alpha (TNF-alpha) in experimental herpes simplex virus type-1 (HSV-1)-induced chorioretinitis of mouse eye.

METHODS

50 BALB/c mice were randomly divided into two different groups (25 mice in each group). The Von Szily model was induced in mice by inoculating 1x10(5) plaque-forming units of HSV-1 (KOS strain) into the anterior chamber of the right eye. In one group, FITC-labeled ASON targeting TNF-alpha was injected subconjunctively into the left eye on days -1, 1, and 4, whereas phosphate buffer was used in the same way on the same days in another group. The clinical appearances were observed after infection each day and the eyes were examined histologically. The TNF-alpha content of retina and choroid were measured by ELISA.

RESULTS

After infection, acute inflammation appeared in the right eye of both groups. As for the non-inoculated eye, the inflammation in the ASON group was significantly decreased compared to the PBS group. The number of inflammatory cells in the ASON group was significantly lower than in the PBS group, especially in the choroid, retina and ciliary body. The TNF-alpha content in the choroid and retina of the ASON group was diminished.

CONCLUSION

The results suggested that TNF-alpha ASON reduced the content of TNF-alpha in mouse eyes, and this topical treatment decreased the inflammatory reaction. It may be an effective method for treating HSV-1-induced chorioretinitis in the clinic.