Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate.
OBJECTIVE
The purpose of the study is to determine the effect of exogenous vascular endothelial growth factor (VEGF) on the primate retina and its vasculature.


METHODS
Ten eyes of five animals were studied. Physiologically relevant amounts of the 165 amino acid isoform of human recombinant VEGF were injected into the vitreous of six healthy cynomolgus monkey eyes. Inactivated human recombinant VEGF or vehicle was injected into four contralateral control subject eyes. Eyes were assessed by slit-lamp biomicroscopy, tonometry, fundus color photography, fundus fluorescein angiography, light microscopy, and immunostaining with antibodies against proliferating cell nuclear antigen and factor VIII antigen.


RESULTS
All six bioactive VEGF-injected eyes developed dilated, tortuous retinal vessels that leaked fluorescein. Eyes receiving multiple injections of VEGF developed progressively dilated and tortuous vessels, venous beading, edema, microaneurysms, intraretinal hemorrhages and capillary closure with ischemia. The severity of the retinopathy correlated with the number of VEGF injections. None of the four control eyes exhibited any abnormal retinal vascular changes. The endothelial cells of retinal blood vessels were proliferating cell nuclear antigen positive only in the bioactive VEGF-injected eyes.


CONCLUSIONS
Vascular endothelial growth factor is sufficient to produce many of the vascular abnormalities common to diabetic retinopathy and other ischemic retinopathies, such as hemorrhage, edema, venous beading, capillary occlusion with ischemia, microaneurysm formation, and intraretinal vascular proliferation.
Tolentino
M J
MJ
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston 02114, USA.
Miller
J W
JW
Gragoudas
E S
ES
Jakobiec
F A
FA
Flynn
E
E
Chatzistefanou
K
K
Ferrara
N
N
Adamis
A P
AP
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000209:etiology* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D007124:Immunoenzyme Techniques; D007267:Injections; D007511:Ischemia / Q000209:etiology* / Q000473:pathology; D008222:Lymphokines / Q000502:physiology*; D008252:Macaca fascicularis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011994:Recombinant Proteins; D012164:Retinal Diseases / Q000209:etiology* / Q000473:pathology; D012166:Retinal Hemorrhage / Q000209:etiology* / Q000473:pathology; D015861:Retinal Neovascularization / Q000209:etiology* / Q000473:pathology; D012171:Retinal Vessels / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014822:Vitreous Body
D016228:Endothelial Growth Factors; D008222:Lymphokines; D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005169:Factor VIII