Abstract
Purpose::
We have recently developed three transgenic models of retinal neovascularisation with different levels of VEGF expression which correlated with the degree of damage to the retinal vasculature. trVEGF029 had either low or medium VEGF levels and damage to the retinal vasculature which was, respectively, either mild or moderate; VEGF levels in trVEGF056 were high and damage was severe. Here we compare the damage observed within the retinal vasculature in each model with that in the choroid.
Methods::
The severity of retinal neovascularisation in each model was confirmed by fundus fluorescein photography (FFA). We used confocal microscopy of Griffonia simplicifolia lectin-stained wholemounts to reveal the retinal vasculature and scanning electron microscopy of Mercox corrosion casts to examine the choroidal vasculature.
Results::
In transgenics, FFA confirmed vascular leakage which was mild, moderate or severe in the three models. Similarly, analysis of the retinal vasculature showed changes including microaneurysms, leukostasis and capillary dropout which were progressively worse in the mild, moderate and severe phenotypes. Changes within the choroid included mircoanuerysms, capillary constrictions and dropout within the capillaries of the choriocapillaris; within the major vessels, tortuosity and loops were observed while loss of venules and arterioles also occurred. Similar to the retinal vasculature, damage within the choroid was progressively worse in the mild, moderate and severe phenotypes.
Conclusions::
Despite the lack of diabetes in our models, choroidal abnormalities closely mimicked those seen in human diabetic retinopathy. Furthermore, the severity of choroidal damage in our models correlated with extent of retinal vascular leakage, i.e. increasing VEGF levels induced greater damage in both the retinal and choroidal vasculatures. The findings indicate that varying levels of VEGF trigger graded pathophysiological changes in both vascular beds. We suggest that the level of VEGF expression may contribute to different degrees of vascular damage in human diabetes and that control of VEGF and/or other angiogenic factors could significantly improve management of diabetic retinopathy patients.
Keywords: transgenics/knock-outs • neovascularization