Abstract
Purpose: :
To test the efficacy of a novel peptide inhibitor of HSV-1 (TAT-Cdo) in a murine model of herpetic keratitis and evaluate four different formulations of the peptide.
Methods: :
The TAT-Cd0 peptide was formulated (1 mg/ml) in PBS, artificial tears, 2% methylcellulose in PBS (gel), or an Aquaphor/mineral oil/ water cream. Vehicle only groups were also included. Micewere infected with 1 X 105 PFU of HSV-1 strain KOS following corneal scarification and treated 5 times per day starting within 4 hrs. of infection. Treatments were continued for 7 days. The severity of blepharitis, corneal clouding, and neovascularization was scored every other day beginning on day 1 post-infection through day 15. Viral tear film samples were collected on the day of scoring prior to initiation of treatment and titers were determined by plaque assay on Vero cell monolayers.
Results: :
There was a significant reduction in blepharitis severity beginning on day 5 for the PBS, tears, and gel formulations. The cream formulation reduced the blepharitis scores but the differences were not significant. For both corneal clouding and neovascularization, all 4 formulations significantly reduced the severity of disease beginning at day 5 or day 9 respectively. Treatment with vehicle only did not significantly reduce the severity of disease. All 4 formulations reduced viral titers by 1.5 logs on day 1 (p<0.05) and virus cleared faster (day 9) in mice treated with the PBS, tears, and gel formulations.
Conclusions: :
The TAT-Cdo peptide was effective in treating HSV-1 keratitis suggesting that the peptide warrants further development. Treatment with vehicle only did not significantly reduce the severity of ocular disease. The peptide, which is cationic, was equally effective in various aqueous formulations indicating that there is flexibility with regard to the presence of excipients.
Keywords: herpes simplex virus • keratitis • antiviral drugs