Recombinant human basic fibroblast growth factor (Rh-bFGF) in three different wound models in rabbits: corneal wound healing effect and pharmacology.
Prior to a clinical trial in humans, we studied the effect and pharmacological distribution of recombinant human basic fibroblast growth-factor (Rh-bFGF) in vivo. Healing experiments on de-epithelialized rabbits corneas (n = 24 animals) compared the efficacy of three bFGF doses to controls and revealed a significantly increased healing rate for both 200 ng and 500 ng per application Rh-bFGF treatment groups compared to the control groups. To assess possible side effects of Rh-bFGF (500 ng topically applied for up to 7 days, twice daily), ten rabbits were involved in a model of an anterior keratectomy wound (performed with Draeger's roto-keratome to a depth of 0.15 mm). Light microscopy of thin sections of treated corneas showed an increased fibrogenesis in the anterior stroma with a more pronounced activation of keratocytes. No evidence for abnormal neovascularization or inflammation was observed when compared to control corneas. Ocular penetration and systemic distribution of topically applied labelled 125I FGF was assessed in three models (iodine vapour epithelial burn, anterior keratectomy and penetrating autokeratoplasty) in 24 rabbits. No intraocular penetration of bFGF occurred as shown by direct gamma counting. Macroautoradiography showed a selective labelling of epithelial basement membrane when denuded and intact, as previously described. Evidence for systemic absorption of breakdown products was confirmed by heparin-sepharose chromatography of blood and urine samples. Under these conditions, we suggest that topical Rh-bFGF promotes corneal wound healing without morphological adverse reaction or intraocular and systemic penetration.
Rieck
P
P
INSERM U 118-CNRS UA 630, Unité de Recherches Gérontologiques/Association Cl. Bernard, Paris, France.
Assouline
M
M
Savoldelli
M
M
Hartmann
C
C
Jacob
C
C
Pouliquen
Y
Y
Courtois
Y
Y
D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005126:Eye Burns / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000493:pharmacokinetics / Q000494:pharmacology*; D015948:Keratoplasty, Penetrating; D008297:Male; D011817:Rabbits; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2