Abstract
Purpose: :
To characterize and compare the natural history of the Yucatan Mini-swine and rabbit model of retinal and choroidal neovascularization.
Methods: :
Yucatan Mini-swine (n=5), Dutch Belt (n = 12) and White New Zealand rabbits (n = 12) were injected subretinally with Matrigel containing a mixture of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Slit lamp, indirect ophthalmoscopy, fundus color photography and fluorescein angiography (FA) demonstrated in vivo the choroidal and retinal vascular changes. Grading of fluorescein angiography images followed qualitative and quantitative clinical standards, where lesions were graded according to type, size and severity. Animals were followed for 45 days or longer, when indicated.
Results: :
In both species, the subretinal injection of matrigel with VEGF and bFGF led to severe and sustained retinal vascular tortuosity and dilation changes up to 4 weeks. In Dutch Belt rabbits, the course of the retinal neovascularization was more severe, leading to proliferative vitreoretinopathy and tractional retinal detachment associated or not to vitreous hemorrhage. In rabbits and minipigs the early findings with respect to the subretinal matrigel bleb consisted of a diffuse subretinal hyperfluorescence, which lasted until late phase FA at early time points, but tended to subside after 4 weeks. Organized subretinal lesions resembling fibrovascular nets could be seen after 15 days post-induction of CNV. These lesions showed increased hyperfluorescence at late phases even after 4 weeks post-induction. In minipigs the subretinal blebs tended to organize and progress into concentric fibrotic lesions. Bevacizumab treatment in both the swine and rabbit models led to decreased retinal vascular changes. In both species, it appeared that the effect of bevacizumab was more prominent in more superficial lesions.
Conclusions: :
Matrigel in combination to angiogenic growth factors triggers a retinal and choroidal neovascular response after subretinal injection in both the mini-swine and rabbit models. This can offer the opportunity for testing new drugs that interfere with angiogenic cascade and CNV healing fibrotic response. Further studies utilizing new drugs as well as approved anti-angiogenic and anti-inflammatory drugs can combine efficacy testing with pharmacokinetics and toxicity evaluation in two non-primate species.
Keywords: choroid: neovascularization • retinal neovascularization • age-related macular degeneration