Generation of transgenic mice with mild and severe retinal neovascularisation.
OBJECTIVE
To generate a mouse model for slow progressive retinal neovascularisation through vascular endothelial growth factor (VEGF) upregulation.


METHODS
Transgenic mice were generated via microinjection of a DNA construct containing the human VEGF165 (hVEGF) gene driven by a truncated mouse rhodopsin promoter. Mouse eyes were characterised clinically and histologically and ocular hVEGF levels assayed by ELISA.


RESULTS
One transgenic line expressing low hVEGF levels showed mild clinical changes such as focal fluorescein leakage, microaneurysms, venous tortuosity, capillary non-perfusion and minor neovascularisation, which remained stable up to 3 months postnatal. Histologically, there were some disturbance and thinning of inner and outer nuclear layers, with occasional focal areas of neovascularisation. By contrast, three other lines expressing high hVEGF levels presented with concomitantly severe phenotypes. In addition to the above, clinical features included extensive neovascularisation, haemorrhage, and retinal detachment; histologically, focal to extensive areas of neovascularisation associated with retinal folds, cell loss in the inner and outer nuclear layers, and partial retinal detachment were common.


CONCLUSIONS
The authors generated four hVEGF overexpressing transgenic mouse lines with phenotypes ranging from mild to severe neovascularisation. These models are a valuable research tool to study excess VEGF related molecular and cellular changes and provide additional opportunities to test anti-angiogenic therapies.
Lai
C-M
CM
Centre for Ophthalmology and Visual Science, The University of Western Australia, Nedlands, Australia. mlai@cyllene.uwa.edu.au
Dunlop
S A
SA
May
L A
LA
Gorbatov
M
M
Brankov
M
M
Shen
W-Y
WY
Binz
N
N
Lai
Y Ky
YK
Graham
C E
CE
Barry
C J
CJ
Constable
I J
IJ
Beazley
L D
LD
Rakoczy
E P
EP
D000818:Animals; D003930:Diabetic Retinopathy / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D005451:Fluorescein Angiography / Q000379:methods; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics*; D010641:Phenotype; D012163:Retinal Detachment / Q000235:genetics / Q000473:pathology; D012166:Retinal Hemorrhage / Q000235:genetics / Q000473:pathology; D015861:Retinal Neovascularization / Q000235:genetics* / Q000473:pathology; D012171:Retinal Vessels / Q000473:pathology / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A