Effects of rat anti-VEGF antibody in a rat model of corneal graft rejection by topical and subconjunctival routes.
OBJECTIVE
To compare the effect of a rat anti-VEGF antibody, administered either by topical or subconjunctival (SC) routes, on a rat model of corneal transplant rejection.


METHODS
Twenty-four rats underwent corneal transplantation and were randomized into four treatment groups (n=6 in each group). G1 and G2 received six SC injections (0.02 ml 10 µg/ml) of denatured (G1) or active (G2) anti-VEGF from Day 0 to Day 21 every third day. G3 and G4 were instilled three times a day with denatured (G3) or active (G4) anti-VEGF drops (10 µg/ml) from Day 0 to Day 21. Corneal mean clinical scores (MCSs) of edema (E), transparency (T), and neovessels (nv) were recorded at Days 3, 9, 15, and 21. Quantification of neovessels was performed after lectin staining of vessels on flat mounted corneas.


RESULTS
Twenty-one days after surgery, MCSs differed significantly between G1 and G2, but not between G3 and G4, and the rejection rate was significantly reduced in rats receiving active antibodies regardless of the route of administration (G2=50%, G4=66.65% versus G1 and G3=100%; p<0.05). The mean surfaces of neovessels were significantly reduced in groups treated with active anti-VEGF (G2, G4). However, anti-VEGF therapy did not completely suppress corneal neovessels.


CONCLUSIONS
Specific rat anti-VEGF antibodies significantly reduced neovascularization and subsequent corneal graft rejection. The SC administration of the anti-VEGF antibody was more effective than topical instillation.
Université Paris Descartes; Faculté de Médecine, Assistance Publique des Hôpitaux de Paris, Hôtel-Dieu Hospital, Department of Ophthalmology, Paris, France.
Nicolas
N
Rocher
Francine
F
Behar-Cohen
Jean-Antoine C
JA
Pournaras
Marie-Christine
MC
Naud
Jean-Claude
JC
Jeanny
Laurent
L
Jonet
Jean-Louis
JL
Bourges
D000818:Animals; D003315:Cornea / Q000276:immunology*; D016510:Corneal Neovascularization / Q000517:prevention & control; D016039:Corneal Transplantation / Q000379:methods*; D004487:Edema / Q000473:pathology; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D008297:Male; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000276:immunology*
D042461:Vascular Endothelial Growth Factor A
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