The effect of roscovitine on herpetic keratitis.
To determine the effect of roscovitine, a potent antiviral in tissue culture administered intramuscularly to rabbits or by eye drops to mice for the treatment of herpetic keratitis this study was commenced.New Zealand white rabbits infected with McKrae strain herpesvirus (HSV-1) were treated twice a day with 10mg Roscovitine or vehicle from day 3 to 7, or 1% trifluridine eye drops five times a day. Severity of keratitis was graded daily by a masked observer. ICR strain mice were randomized into 14 groups. Both corneas of the mice were scarified with a 25-gauge needle, and were inoculated with the KOS strain of HSV-1. Roscovitine was dissolved in Cremophor((R)) and tissue culture medium. Group 1A, 1B, 2A, and 2B mice were treated eight times daily with either 800 micro M Roscovitine or its vehicle. Trifluridine treated animals (groups 3A and 3B) received topical treatment five times daily. In groups 1A-3B, the treatment was begun two days prior to or two days after viral inoculation. Mice were examined on days 2, 3, 5, and 9 after infection. In rabbits, the severity of keratitis in animals treated with intramuscular roscovitine was not significantly different from that in vehicle-treated animals except on day 7 (p=0.0460). In mice, there was no significant difference between roscovitine and vehicle treatment at any time point studied. However, the trifluridine treated mice had significantly lower scores compared to the roscovitine or vehicle-treated mice. Although roscovitine dramatically suppresses viral replication in tissue culture studies, in vivo this drug failed to alter the course of HSV keratitis in rabbits or mice. Considering high cost of roscovitine and the poor efficacy in these experiments, we feel that roscovitine is not feasible antiviral agent for today.
Department of Ophthalmology, LSU Eye Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans, LA 70112, USA. avunduk@ttnet.net.tr
Avni Murat
AM
Avunduk
Emily D
ED
Varnell
Herbert E
HE
Kaufman
D000704:Analysis of Variance; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy*; D018259:Herpesvirus 1, Human; D007273:Injections, Intramuscular; D007634:Keratitis / Q000188:drug therapy* / Q000821:virology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009883:Ophthalmic Solutions; D011687:Purines / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D000077546:Roscovitine; D017211:Treatment Failure
D000998:Antiviral Agents; D009883:Ophthalmic Solutions; D011687:Purines; D000077546:Roscovitine