Fibroblast growth factor 2, heparin and suramin reduce epithelial ulcer development in experimental HSV-1 keratitis.
BACKGROUND
We have previously shown that basic fibroblast growth factor (FGF-2) enhances corneal epithelial healing in different experimental models in vivo. In order to study the healing effect of this growth factor in pathological conditions of the cornea, we investigated whether topical application of FGF-2 could affect herpes keratitis in rabbits. Since HSV-1 infection is prevented in vitro by incubation with heparin, we also topically applied heparin and suramin, considering the similar interaction of herpes simplex virus and FGF-2 with cell membrane-anchored heparan sulfate.


METHODS
After virus inoculation with a human BEY.2 strain, rabbits were treated with either FGF-2 (200 ng to 2 micrograms/application), heparin (250 micrograms/application) or suramin (250 micrograms/application) 4 times daily until day 14. Acyclovir and placebo administrations served as controls (n = 48 rabbits). Computerized ulcer surface analysis, clinical observations and virus recovery assays were performed.


RESULTS
Topical FGF-2, heparin and suramin treatment revealed a significant reduction in peak ulcer sizes, and complete epithelial healing was achieved earlier than in placebo-treated corneas. However, no significant antiviral effect of FGF-2, heparin and suramin was detectable in plaque assays from conjunctival swabs.


CONCLUSIONS
These experiments demonstrate that FGF-2 is effective in promoting herpetic epithelial ulcer healing, either due to its proliferative effects on epithelial cells or indirectly by occupying the sites on cell surface heparan sulfate necessary for the attachment of the virion. The latter mechanism of action is presumably the reason for the similar effect of heparin and suramin.
Rieck
P
P
Department of Ophthalmology, Charité-Virchow Medical Faculty, Humboldt University Berlin, Germany.
Denis
J
J
Peters
D
D
Hartmann
C
C
Pouliquen
Y
Y
Courtois
Y
Y
D000212:Acyclovir / Q000008:administration & dosage; D000287:Administration, Topical; D000818:Animals; D016510:Corneal Neovascularization / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary; D003318:Corneal Opacity / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D004359:Drug Therapy, Combination; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D015828:Eye Infections, Viral / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D009883:Ophthalmic Solutions; D011817:Rabbits; D013498:Suramin / Q000008:administration & dosage* / Q000009:adverse effects; D013666:Tears / Q000821:virology; D014945:Wound Healing / Q000187:drug effects
D009883:Ophthalmic Solutions; D016222:Fibroblast Growth Factor 2; D013498:Suramin; D006493:Heparin; D000212:Acyclovir