Natural history of choroidal neovascularization induced by vascular endothelial growth factor in the primate.
BACKGROUND
A new model of choroidal neovascularization (CNV) has been developed in the primate by implanting vascular endothelial growth factor (VEGF)-impregnated microspheres in the subretinal space.


METHODS
CNV was induced in Macaca mulatta monkeys by implanting VEGF-impregnated gelatin microspheres in the subretinal space. Progression of CNV was followed for 24 weeks after surgery using fluorescein angiography. Eyes were enucleated at various time points, and lesions were evaluated for evidence of CNV by light microscopy and by immunohistochemical staining.


RESULTS
CNV developed in 12 (92%) of 13 eyes. Fluorescein leakage was first observed in the 2nd postoperative week and was apparent for the following 12 weeks. CD31 staining for endothelial cells was first observed at day 7 and was evident for the following 8 weeks. Glial fibrillary acidic protein staining revealed a glial adhesion between the proliferative membrane and the retina at 6 weeks after implantation. Smooth muscle actin-positive cells were found a +2 weeks and remained prominent for at least the next 6 weeks. Cytokeratin-positive retinal pigment epithelial (RPE) cells, first identified in the proliferative membrane at day 3, predominated throughout the growth of the membrane. Macrophages (RAM-II positive) were present at day 3 but were no longer observed after day 7.


CONCLUSIONS
In monkeys, subretinal implantation of VEGF-impregnated gelatin microspheres leads to the development of CNV. Early, disciform and reparative stages of CNV were observed, similar to those seen in humans. This model will be useful for studying the pathogenesis of CNV and for evaluating potential treatment strategies.
Cui
J Z
JZ
Doheny Eye Institute, Los Angeles, CA 90033, USA.
Kimura
H
H
Spee
C
C
Thumann
G
G
Hinton
D R
DR
Ryan
S J
SJ
D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D020256:Choroidal Neovascularization / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004343:Drug Implants; D016228:Endothelial Growth Factors / Q000633:toxicity*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000378:metabolism; D008222:Lymphokines / Q000633:toxicity*; D008253:Macaca mulatta; D008863:Microspheres; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012160:Retina / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000199:Actins; D015415:Biomarkers; D004343:Drug Implants; D016228:Endothelial Growth Factors; D005904:Glial Fibrillary Acidic Protein; D008222:Lymphokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D007633:Keratins