Experimental corneal neovascularisation using sucralfate and basic fibroblast growth factor.
OBJECTIVE
To develop a non-inflammatory model of both acute and chronic angiogenesis in the rabbit cornea using a known directly angiogenic cytokine.


METHODS
Pellets made of the slow-release polymer Hydron (polyhydroxyethylmethacrylate) and containing sucralfate and/or basic fibroblast growth factor (basic-FGF) were implanted into rabbit corneas. The neovascular response to the implantation of pellets containing basic-FGF alone, sucralfate alone or a titration of basic-FGF in the presence of a constant amount of sucralfate was measured. The role of inflammation in the neovascular response was also investigated.


RESULTS
The addition of sucralfate to the pellets led to the sustained release of basic-FGF resulting in a predictable and aggressive neovascular response with a low dose of basic-FGF that by itself was unable to elicit neovascularisation. At a dose of 500 ng per pellet, approximately one-third of the surface area of the cornea was vascularised within eight days of implantation. Minimal or no vascularisation occurred with the same dose of basic-FGF without sucralfate. While this dose of basic-FGF induced corneal oedema, only minimal inflammation was observed and the response was unaffected by ionising radiation. A less aggressive though still robust neovascular response with no or only minimal oedema was observed when the dose was lowered to 50 ng of basic-FGF per pellet. Some induced vessels persisted for more than three months.


CONCLUSIONS
This is an inexpensive in vivo model of angiogenesis with the advantages of the neovascularisation being aggressive, predictable, persistent, unassociated with an obvious inflammatory response and induced by the sustained release of an agent known to have a direct stimulatory action on endothelial cells.
Department of Surgery, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115, USA.
M S
MS
Loughman
K
K
Chatzistefanou
E M
EM
Gonzalez
E
E
Flynn
A P
AP
Adamis
Y
Y
Shing
R J
RJ
D'Amato
J
J
Folkman
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D003315:Cornea / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000473:pathology*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000633:toxicity*; D011817:Rabbits; D013392:Sucralfate / Q000633:toxicity*
D003692:Delayed-Action Preparations; D004338:Drug Combinations; D016222:Fibroblast Growth Factor 2; D013392:Sucralfate