The antimicrobial agent C31G is effective for therapy for HSV-1 ocular keratitis in the rabbit eye model

Abstract

1. Summary The amphoteric C31G solution contains equimolar alkyl dimethlyglycine and alkyl dimethyl amine oxide buffered with citric acid. C31G acts as a broad spectrum antiviral and an antibacterial. No previous in vivo studies have been done to test C31G in an animal model of HSV-1 ocular keratitis. We assessed the anti-herpetic activity of C31G in the rabbit eye model using three treatment groups: (1) 1% trifluorothymidine (TFT); (2) 0.25% C31G plus 0.5% hydroxypropyl methylcellulose (HPMC); and (3) 0.5% HPMC. Scarified rabbit corneas were inoculated with the HSV-1 strain McKrae. On post inoculation (PI) day 3, rabbits were placed in three balanced groups based on slit-lamp examination (SLE) scores. Treatment began on PI day 3, five times a day for five consecutive days. In addition to the daily, masked SLE scoring, the eyes were assessed daily for stromal opacity, scleral inflammation, neovascularization, eyelid inflammation, inflammatory discharge, and epiphora. C31G and TFT were very effective in reducing the lesions and pathogenesis associated with HSV-1 ocular keratitis. The vehicle control SLE scores were significantly higher, proving that the vehicle did not effectively treat HSV-1 keratitis. C31G has valuable potential to treat herpetic keratitis as well as other herpetic topical lesions in humans.

Ex vivo model of herpes simplex virus type I dendritic and geographic keratitis using a corneal active storage machine

“…There seems to be only one reference, dating from 1970, which also formulated this hypothesis but on a very different model. The authors used a model of penetrating keratoplasty in rabbits with scraping of the donor epithelium [ 39 ]. In this model the peripheral nerves persist and, as the authors point out, regeneration of the intraepithelial nerves is possible within a few days, which is not true of our model.…”

“…Its initial intracellular penetration must thus be carried out on basal or intermediate epithelial cells, which are metabolically more active. This scarification was already used in several ex vivo human [15,18] and porcine [21,22] models and also in in vivo mice and rabbit models [36][37][38][39][40], in particular to promote infection on a healthy cornea, where the virus is quickly eliminated by eyelid blinking.…”

Herpes Simplex Virus-1 Induced Serotonin-Associated Metabolic Pathways Correlate With Severity of Virus- and Inflammation-Associated Ocular Disease

“…Control and TFT treated rabbits in all studies followed an identical protocol. Prior to inoculation, the number of viral plaque-forming units (PFU) was determined with a standard plaque assay procedure with Vero cells ( Sanchez et al, 2012 , 2016 ; Hill et al, 2013 , 2014 ). New Zealand White (NZW) rabbits (2–3 kg) obtained from RSI Robinson Services Rabbitry were inoculated with 1 × 10 4 PFU of HSV-1 McKrae in each eye following mild scarification of the central cornea in a 4 by 4 grid pattern with a blunted 28-gauge needle.…”

“…Analyzed animals had been treated topically q.i.d with 50 μl of either 0.5% Carboxymethlylcellulose (CMC) BSS or 0.5% TFT in 0.5% CMC BSS. Clinical disease parameters, including epiphora/tearing, inflammatory discharge, corneal epithelium, corneal inflammation, stromal inflammation, corneal neovascularization, scleral injection/conjunctivitis, blepharitis, and fluorescent slit lamp evaluation were assessed daily in a masked fashion as previously described ( Clement et al, 2011 ; Hill et al, 2012 , 2013 , 2014 ; Webre et al, 2012 ). In addition, corneal thickness was measured using a Reichert iPac Pachymeter.…”