Pharmacokinetic and autoradiographic studies of basic fibroblast growth factor on de-epithelialized and intact rabbit eye.
In a previous work, we showed and compared the wound healing properties of aFGF and bFGF topically administered on totally de-epithelialized rabbit corneas. Pharmacokinetic and autoradiographic studies were then performed to investigate the sites of accumulation of bFGF in ocular structures, both on de-epithelialized and intact rabbit eyes. After one single instillation of 125I-bFGF, all the ocular structures were dissected and the measurement of the radioactivity allowed to establish kinetic curves. The results showed a very important and early fixation of bFGF on denuded cornea (10 minutes) and a posterior distribution of the drug between 10 and 30 minutes. A second accumulation of bFGF in the anterior segment appeared 8 hours after application and then decreased till the 48th hour. These findings were confirmed by the macroautoradiographies and the microautoradiographies pointed out the fixation of bFGF not only at the location of the Bowman membrane, but also on the corneal endothelium. These experiments also demonstrated the systemic diffusion of bFGF into the untreated controlateral eye. The integrity of bFGF in the cornea and other structures was then confirmed by SDS PAGE followed by autoradiography. In the intact eye, bFGF was shown to penetrate in extremely low amounts, illustrating the major role of the corneal barrier. For a therapeutic use bFGF may be recommended as an efficient wound healing agent for epithelial but also endothelial defects. Its eventual unwanted side effects must be kept in mind to perfect an efficient low dose and short term clinical treatment.
Fredj-Reygrobellet
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D
Laboratoire de Pharmacologie, Faculté de Médecine, Nice, France.
Elena
P P
PP
Moenner
M
M
Baudouin
C
C
Ettaiche
M
M
Barritault
D
D
Lapalus
P
P
D000818:Animals; D001345:Autoradiography / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel; D004848:Epithelium / Q000378:metabolism; D005123:Eye / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008099:Liver / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins; D013997:Time Factors; D014018:Tissue Distribution
D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors