Application of FGF-2 to modulate herpetic stromal keratitis.
OBJECTIVE
Herpetic stromal keratitis (SK) is a tissue destructive eye lesion caused by infection of herpes simplex virus-1 (HSV-1). One step by which HSV-1 enters the cell is through binding to surface heparan sulfate proteoglycans (HSPG), a process that can be inhibited by fibroblast growth factor 2 (FGF-2). The current study examined the effect of FGF-2 application on the outcome of ocular HSV infection.


METHODS
Vero cells were infected with HSV-1 after preincubation with FGF-2 protein, and viral infectivity was determined by plaque reduction assay. In an in vivo study, mice were ocularly treated with FGF-2 before (plasmid DNA) or after (recombinant protein) HSV-1 infection, and SK lesion severity was observed.


RESULTS
Whereas FGF-2 had excellent antiviral effects in vitro, it was without significant inhibitory effects when given as plasmid DNA encoding FGF-2 (100 microg/application) onto the cornea of the susceptible mouse (BALB/c) before virus infection. Only minor antiviral effects of FGF-2 in vivo were initially observed. Interestingly, topical treatment of recombinant FGF-2 protein (50 ng, two times daily until day 10 postinfection) into HSV-1-infected corneas significantly reduced SK lesion severity and incidence, presumably by promoting epithelial ulcer healing.


CONCLUSIONS
These results suggest that treatment of FGF-2 has therapeutic effects on herpetic SK progression via its role in wound healing.
Kim
Bumseok
B
Department of Microbiology and Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee 37996-0845, USA.
Lee
Sujin
S
Kaistha
Shilpa Deshpande
SD
Rouse
Barry T
BT
D000287:Administration, Topical; D000818:Animals; D002522:Chlorocebus aethiops; D003319:Corneal Stroma / Q000187:drug effects* / Q000821:virology; D004279:DNA, Viral; D005260:Female; D018259:Herpesvirus 1, Human / Q000302:isolation & purification / Q000502:physiology*; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014709:Vero Cells / Q000187:drug effects / Q000821:virology; D019562:Viral Load; D014945:Wound Healing / Q000187:drug effects
D004279:DNA, Viral; D011994:Recombinant Proteins; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2