Ocular penetration of anti-herpes simplex virus type 1 anticode oligodeoxyribonucleoside methylphosphonate (d-OMP) in an animal model

Purpose. To demonstrate the ocular penetration of anti-herpes simplex virus type 1 (HSV-1) anticode oligodeoxyribonucleoside methylphosphonate (d-OMP) in a rabbit model. Previous studies have shown this d-OMP to selectively inhibit HSV-1 replication in virus infected cells. Methods. A 50 μM solution containing a d-OMP whose structure is complementary to the splice junction of HSV-1 immediate early pre-mRNA 4 and 5 was administered topically in rabbit eyes. The d-OMP had been tagged with a fluorescent marker, a BODIPY (bordifluoropyrromethene) derivative. The d-OMP was instilled into the NZW rabbit eyes at 5 minute intervals for a total of 3 doses (35 μl per dose). Fellow eyes of rabbits which received only topical saline in a similar fashion, served as controls. Animals were sacrificed at 15 minutes, 30 minutes, and 45 minutes respectively after the first dosing and their corneas removed for frozen section. The frozen sections were then immediately examined under an epifluorescent microscope. Results. A layer of fluorescence was observed in the superficial epithelium as early as 15 minutes after the first dose of d-OMP. This fluorescent layer was still present in the corneal epithelium at 30 minutes. 45 minutes after the first dosing, the penetration of fluorescence had increased, although the total fluorescence appeared less intense and more diffuse in the deeper layers of epithelium. No fluorescence was observed in frozen sections of control eyes. Conclusion. This suggests that d-OMP penetrates fairly rapidly into the rabbit cornea when administered topically. d-OMP at the active site may have a potentially useful role as an antiviral agent for the clinical treatment of herpes simplex epithelial keratitis.