Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate.
OBJECTIVE
To determine if the angiogenic peptide vascular endothelial growth factor (VEGF) is required for retinal ischemia-associated iris neovascularization in a nonhuman primate.


METHODS
Laser retinal vein occlusion was used to produce retinal ischemia in 16 eyes of eight animals (Macaca fascicularis). Eyes were randomized to treatment every other day with intravitreal injections of either a neutralizing anti-VEGF monoclonal antibody or a control monoclonal antibody of the same isotype. Serial iris fluorescein angiograms were assessed using a standardized grading system and masked readers. Retinal VEGF and placental growth factor expression were assessed by Northern blotting. The specificity of the antibodies was determined in capillary endothelial cell proliferation assays prior to intravitreal injection.


RESULTS
Zero of eight eyes receiving the neutralizing anti-VEGF antibodies developed iris neovascularization. Five of eight control antibody-treated eyes developed iris neovascularization. The difference was statistically significant (P = .03). Intravitreal antibody injection did not impair the ability of the ischemic retina to increase VEGF messenger RNA expression. The anti-VEGF antibodies specifically inhibited VEGF-driven capillary endothelial cell proliferation in vitro.


CONCLUSIONS
These data demonstrate that VEGF is required for iris neovascularization in an adult nonhuman primate eye. The inhibition of VEGF is a new potential therapeutic strategy for the treatment of ocular neovascularization.
Adamis
A P
AP
Department of Opthalmology, Massachusetts Eye and Ear Infirmary, Boston, USA.
Shima
D T
DT
Tolentino
M J
MJ
Gragoudas
E S
ES
Ferrara
N
N
Folkman
J
J
D'Amore
P A
PA
Miller
J W
JW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015152:Blotting, Northern; D002199:Capillary Permeability; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D005451:Fluorescein Angiography; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D007498:Iris / Q000098:blood supply* / Q000473:pathology; D007511:Ischemia / Q000150:complications* / Q000378:metabolism; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D008252:Macaca fascicularis; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D012160:Retina / Q000378:metabolism; D012170:Retinal Vein Occlusion / Q000150:complications* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D016228:Endothelial Growth Factors; D015699:HIV Envelope Protein gp120; D008222:Lymphokines; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000072483:Placenta Growth Factor