VEGF-induced choroidal damage in a murine model of retinal neovascularisation.
OBJECTIVE
Photoreceptor-specific upregulation of vascular endothelial growth factor (VEGF) in a transgenic mouse model (Kimba) of retinal neovascularisation induces retinal vascular damage which appears similar to that in diabetic retinopathy. Here we have determined whether the choroidal vasculature is also affected in Kimba.


METHODS
Kimba mice were assessed with fundus fluorescein angiography for mild, moderate or severe retinal vascular leakage prior to preparation of choroidal corrosion casts for quantitative analysis using scanning electron microscopy. VEGF was located immunohistochemically.


RESULTS
Choroidal abnormalities included microaneurysms, constriction, shrinkage and dropout in the capillaries and tortuosity and loops in the arteries and veins which were similar to those observed in corrosion casts of the human choroid in diabetes. Similar to human diabetes, choroidal neovascularisation was not observed. The severity of choroidal damage correlated with the extent of retinal vascular leakage. In addition to the expected presence of VEGF in photoreceptors, VEGF was also detected in the pigment epithelium and choroid in the transgenic mice.


CONCLUSIONS
We show that elevated retinal VEGF levels trigger pathophysiological changes in the choroid. We suggest that therapies to prevent vascular damage in diabetes must target both the retinal and choroidal vasculatures.
School of Animal Biology, The University of Western Australia, Perth, Australia.
L B G
LB
Tee
M A
MA
Penrose
J E
JE
O'Shea
C-M
CM
Lai
E P
EP
Rakoczy
S A
SA
Dunlop
D000818:Animals; D002196:Capillaries / Q000648:ultrastructure; D002829:Choroid / Q000098:blood supply* / Q000737:chemistry / Q000378:metabolism; D016319:Corrosion Casting; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D023421:Models, Animal; D010641:Phenotype; D010857:Pigment Epithelium of Eye / Q000737:chemistry / Q000378:metabolism; D015861:Retinal Neovascularization / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A