In vivo inhibition of lens regrowth by fibroblast growth factor 2-saporin.
OBJECTIVE
To investigate the ability of fibroblast growth factor (FGF) 2-saporin to prevent lens regrowth in the rabbit.


METHODS
Chemically conjugated and genetically fused FGF2-saporin (made in Escherichia coli) were used. Extracapsular extraction of the lens was performed on the rabbit, and the cytotoxin either was injected directly into the capsule bag or was administered by FGF2-saporin-coated, heparin surface-modified (HSM) polymethylmethacrylate intraocular lenses. The potential of the conjugate was checked by slit lamp evaluation of capsular opacification and by measuring crystallin synthesis. Toxin diffusion and sites of toxin binding were assessed by immunohistochemistry. Possible toxicity was determined by histologic analysis of ocular tissues.


RESULTS
FGF2-saporin effectively inhibited lens regrowth when it was injected directly into the capsular bag. However, high concentration of the toxin induced transient corneal edema and loss of pigment in the iris. Intraocular lenses coated with FGF2-saporin reduced lens regrowth and crystallin synthesis without any detectable clinical side effect. After implantation, FGF2-saporin was shown to have bound to the capsules and, to a lesser extent, to the iris; no histologic damage was found on ocular tissues as a result of implantation of drug-loaded HSM intraocular lenses.


CONCLUSIONS
Chemically conjugated (FGF2-SAP) and genetically fused FGF2-saporin (rFGF2-SAP) bound to HSM intraocular lenses can prevent lens regrowth in the rabbit.
Behar-Cohen
F F
FF
Unité de Recherches Gérontologiques, Inserm U 118, Paris, France.
David
T
T
D'Hermies
F
F
Pouliquen
Y M
YM
Buechler
Y
Y
Nova
M P
MP
Houston
L L
LL
Courtois
Y
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000494:pharmacology*; D002386:Cataract / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002387:Cataract Extraction; D002455:Cell Division / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006493:Heparin; D000922:Immunotoxins; D007903:Lens Capsule, Crystalline / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007910:Lenses, Intraocular; D008768:Methylmethacrylates; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D008768:Methylmethacrylates; D010940:Plant Proteins; D011994:Recombinant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D016222:Fibroblast Growth Factor 2; D006493:Heparin; D009699:N-Glycosyl Hydrolases; D000076985:Saporins